Active infection requiring treatment with systemic anti-infectives or major surgery in prior 4 weeks.
Participants may have either extensive or limited cGVHD requiring systemic treatment
Evidence of an active lesion including: plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other cancer requiring concurrent treatment with chemotherapy or radiation therapy; patients not requiring treatment for these lesions are eligible for this protocol
Active or chronic corneal disorder, including but not limited to the following: Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
Psoriasis or eczema not requiring systemic treatment.
Inflammatory eye disease requiring steroid treatment
Active infection requiring IV anti-infective usage within the last 7 days prior to study treatment.
Active or chronic corneal disorder, including but not limited to the following: Sjogren’s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, acquired monocular vision, and any preexisting active conjunctival disease
Active or chronic corneal disorder, history of corneal transplantation, active herpetic keratitis, and active ocular conditions requiring ongoing treatment/monitoring
Malignancy requiring systemic therapy; Note: Kaposi sarcoma limited to the skin is not exclusionary unless requiring systemic chemotherapy
Active gout or inflammatory arthritis requiring treatment
Active or chronic corneal disorder, including but not limited to the following: Sjogren’s syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
No active or co-existing malignancy requiring chemotherapy or radiation within 6 months
Participants with a history of an opportunistic fungal infection or active fungal infection requiring, or at high risk of requiring, prophylactic or treatment with fluconazole, voriconazole or posaconazole
Uncontrolled or active ocular problems (e.g., retinopathy, macular edema, active uveitis, wet macular degeneration) requiring surgery, laser treatment, or intravitreal injections
Acute infection requiring systemic treatment
Ongoing infection requiring systemic treatment
Has history of/active pneumonitis that required/is requiring steroid treatment or had history of/active interstitial lung disease; has an active infection requiring systemic treatment
Has an active infection requiring systemic therapy; antimicrobial prophylaxis will be permitted at the discretion of the treating investigator
Active infection requiring treatment.
Active infection requiring treatment
Requiring active treatment for Toxoplasma gondii infection
Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
Acute active infection requiring treatment should be under control
Patients with active infection requiring systemic antimicrobials
Subject has active infection requiring systemic therapy that has not completely resolved within 14 days prior to start of study treatment.
Serious, concomitant disorder, including active systemic infection requiring treatment, in the opinion of the investigator;
Active infection requiring treatment.
Acute infection requiring systemic treatment
Ongoing or active infection requiring systemic treatment (must be afebrile for >= 48 hours prior to study registration)
Active infection requiring treatment or chronic infection requiring suppressive therapy
Active infection requiring systemic treatment within one week prior to first dose.
Active infection requiring treatment at the time of study treatment initiation
Requiring active treatment for Toxoplasma gondii
Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
Other malignancy requiring active treatment
Any acute medical problems requiring active intervention
Patients with active infection requiring systemic antimicrobials
Patients who have an active 2nd malignancy requiring systemic treatment
Subjects with psoriasis not requiring systemic treatment;
Prior treatment for lymphoid malignancy requiring treatment for progressive disease
Subjects with psoriasis not requiring systemic treatment
Any other malignancy requiring treatment
Active infection requiring treatment
Active infection requiring treatment within two weeks prior to first dose.
The patient has a recently diagnosed active malignancy requiring therapy
Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
History of other primary malignancy requiring systemic treatment within 6 months of protocol enrollment; patients must not have another active malignancy requiring treatment; patients must not be receiving chemotherapy or immunotherapy for another cancer
Other active primary malignancy requiring treatment or limiting survival to =< 2 years prior to registration
Active or chronic corneal disorder, including but not limited to the following:\r\n* Sjogren’s syndrome\r\n* Fuchs corneal dystrophy (requiring treatment)\r\n* History of corneal transplantation\r\n* Active herpetic keratitis\r\n* Active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision
Active systemic hepatitis infection requiring treatment or other clinically active liver disease
Acute active infection requiring treatment.
Acute active infection requiring treatment.
Active uncontrolled infectious diseases requiring treatment
Any serious concomitant illness or infectious disease requiring treatment, or infectious disease not requiring treatment, but with significant risks for myelosuppressive complications associated with chemotherapy.
History of any other malignancy requiring active treatment
Active HSV infection requiring treatment, or requiring intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g. acyclovir)
Other malignancy requiring active treatment at time of study entry
Other active, invasive malignancy requiring ongoing therapy or expected to require systemic therapy
Patients must not have an active infection requiring systemic therapy nor a viral infection requiring intermittent treatment with an antiherpetic drug, other than intermittent topical use
Diabetics requiring insulin treatment
Patients requiring treatment in supine position
Active infection requiring IV anti-infective therapy
Current sexually transmitted infection (STI) requiring treatment (women may participate after adequate treatment, at the discretion of the treating provider)
A serious, concomitant disorder, including active systemic infection requiring treatment
Active infection requiring antimicrobial treatment that would interfere with interpretation of adverse events, cutaneous reactions or efficacy. Treatment of minor concurrent infections should be limited to less than 10 days.
Subjects with psoriasis not requiring systemic treatment
Serious illness requiring systemic treatment and/or hospitalization within 45 days prior to entry
History of active anal disease requiring surgery
Other malignancy diagnosed or requiring treatment within the defined period with specific exceptions
Active other malignancy requiring treatment that would interfere with the assessments of this study
Evidence of other active malignancy requiring treatment
Arrhythmia requiring treatment which is not stabilized by the treatment
Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior cycle 1, day 1
Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.
Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
Serious infection requiring oral or IV antibiotics/antifungals/antivirals and/or hospitalization within 28 days prior to screening\r\n* Patients on prophylactic oral antibiotics, antifungals and antivirals due to prolonged neutropenia in the absence of documented infection are eligible\r\n* Patients who are treated with IV antibiotics for neutropenic fever, are eligible if no infectious etiology was determined and the last dose of antibiotics was >= 7 days from cycle 1, day 1
Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
Uncontrolled infection requiring systemic antibiotics/antivirals/antifungals
Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
Patients with active infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study until resolution of the infection; patients on prophylactic antibiotics, antifungals or antivirals are acceptable
Active infection requiring antibiotics or antifungals within 7 days prior to first dose of study drug
Treatment with intravenous (systemic antibiotics, antivirals, or antifungals) within 14 days prior to start of treatment
Chronic or current active infectious disease requiring systemic antibiotics, antifungals, or antivirals
Subjects with an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis A, B or C infection
Infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks prior to C1D1.
Acute infection requiring treatment (IV antibiotics, antivirals, or antifungals) within 14 days prior to initiation of study
Acute infection requiring systemic anti-infectives, antivirals, or antifungals within two weeks prior to first dose
Patients with an active infection requiring intravenous antivirals, antibiotics or antifungals; patients on prolonged antifungal therapy are still eligible if they are culture negative and biopsy negative in suspected residual radiographic lesions have stabilized or regressed and they meet other organ function criteria
Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Uncontrolled active infection requiring systemic antibiotics, antivirals, or antifungals within one week prior to first dose; prophylactic antimicrobials are permitted
Must not have acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment.
Acute infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within 14 days prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Patients who have an acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to registration are NOT eligible for participation
Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals.
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Active infection requiring antibiotics or antifungals within 7 days prior to first dose of study drug
Active infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks prior to first dose of study drug
Have active serious infection uncontrolled by antibiotics or antifungals
Ongoing or active infection; treatment with systemic antibiotics or antifungals for ongoing or recurrent infection (topical use of antibiotics or antifungals is allowed)
Clinically relevant active infection requiring treatment (antibiotics, antivirals, antifungals)
Acute infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of study
Active infection requiring antibiotics or antifungals within 7 days prior to first dose of study drug
Uncontrolled active infection requiring parenteral antibiotics, antivirals or antifungals within 1 week prior to the first date of study treatment
Acute infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of study
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
Acute active infection requiring treatment (IV antibiotics, antivirals, or antifungals) within 14 days prior to the first day of treatment
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
Presence of an acute infection requiring active treatment with antibiotics/antivirals; prophylactic administration is allowed
No acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to cycle 1 day 1
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to signing consent
Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
Active infection (including HIV/acquired immune deficiency syndrome [AIDS], hepatitis B, or hepatitis C infection) requiring systemic antibiotics, antivirals, or antifungals
Oral or IV antibiotics, antifungals, or antivirals within 1 week, with the exception of prophylactic oral agents. Note: In the event that a subject requires the chronic use of antivirals, Medical Monitor permission is required for entry into the study.
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or active hepatitis B or C infection.
Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
Have an active, clinically significant serious infection requiring intravenous treatment with antibiotics, antivirals, or antifungals.
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose; active infection with concurrent treatment is acceptable only if the patient is clinically stable
Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to C1D1.
Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals, known human immunodeficiency virus infection, or tested positive for active hepatitis B or C infection
Uncontrolled infection; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable
Active uncontrolled infection; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
Uncontrolled infection at the time of enrollment; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
Uncontrolled systemic infection requiring parenteral anti-microbial therapy.
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
Patients who have an uncontrolled infection are not eligible; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable
Uncontrolled active systemic infection or recent infection requiring parenteral anti-microbial therapy
Uncontrolled infection within one week of the first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
Any active infection requiring the use of parenteral anti-microbial agents or that is > Grade 2;
Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungals, and anti-viral agents)
Uncontrolled infection at the time of enrollment; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable
Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable
Presence of GVHD overlap syndrome.
Participants must have acute GVHD of the lower gastrointestinal tract as defined by the clinical impression of the treating physician, requiring systemic treatment; minimum criteria for GI GVHD includes diarrhea of greater than 500 mL/day; biopsy of the GI tract is required for study entry and must confirm the diagnosis of acute GVHD; stool samples to rule out infectious causes of diarrhea, including norovirus, Clostridium difficile and other clinically indicated infections must also be negative; eligibility includes:\r\n* Acute GVHD developing after allogeneic hematopoietic stem cell transplantation (HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood; recipients of non-myeloablative, reduced intensity and myeloablative transplants are eligible\r\n* Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible\r\n* There is no specified time window after day 0 of transplant as acute GVHD is only defined by clinical manifestations\r\n* Patients must have experienced neutrophil engraftment after HSCT as defined by absolute neutrophil counts >= 500 /uL x 3 consecutive measurements\r\n* Platelets >= 10,000 / uL (platelet transfusions are allowed on the same day)\r\n* The presence of hepatic, upper GI and/or cutaneous acute GVHD is permitted\r\n* Steroids can be started up to 7 days prior to the administration of natalizumab
Patients with the entity of acute/chronic GVHD overlap syndromes
If the participant has developed overall grades II-IV acute GVHD, the following criteria must be met to be randomized:
Receiving an investigational GVHD treatment within 28 days of study entry.
Has acute GVHD.
Participants receiving GVHD prophylaxis with drugs other than calcineurin inhibitor, short-course methotrexate, steroids, mycophenolate mofetil, or sirolimus
? Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
Subject with chronic GVHD features (acute/chronic GVHD overlap syndrome or classical chronic GVHD).
Patients can continue to receive other immunosuppressive drugs for treatment of GVHD as determined by their primary team
Patients on other experimental protocols for prevention of acute GVHD
GVHD prophylaxis must include a calcineurin inhibitor combined with methotrexate or mycophenolate.
Patients who develop acute GVHD prior to start of study drug.
Active GVHD or on immunosuppressive medication for GVHD (applies to cohort #2)
Any drug used for GVHD within 4 weeks prior to enrollment
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
Participants may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d
NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day 1
NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea > 556 mL/m2/day, or severe abdominal pain with or without ileus) within 7 days prior to Day 1
Patient is using or plans to use an investigational agent for the prevention of GvHD.
Subjects must be free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment
Patients who develop grade IV acute GVHD or severe chronic GVHD prior to enrollment on the protocol
Has a diagnosis of active GvHD (>= grade I); patients with prior active GvHD that is quiescent (grade 0) at time of entry may be considered
Patients must have no active acute or chronic GVHD
Subjects must be free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment. GVHD status will be determined in conjunction with an evaluation by an oncologist specialized in GVHD diagnosis and management through Seattle Children’s Blood and Cancer Disorders Center
Acute GvHD prophylaxis with methotrexate and tacrolimus
Active grade III-IV classic acute GvHD; subjects with prior resolved acute GvHD on stable doses of immunosuppression at time of enrollment will be permitted
Evidence of classic chronic GvHD or overlap chronic GvHD at time of enrollment
Subjects who participated in a clinical trial of acute GvHD prophylaxis in which chronic GvHD was a secondary end point
Active acute or chronic GVHD of the liver
CRITERIA FOR LYMPHODEPLETING CHEMOTHERAPY AND huJCAR014 TREATMENT: Presence of active acute or chronic GVHD
Patients receiving post-transplant cyclophosphamide as GVHD prophylaxis
Acute or chronic GVHD with ongoing active systemic treatment
Either no evidence of graft versus host disease (GVHD) or minimal clinical evidence of acute GVHD and chronic GVHD while off of systemic immunosuppressive therapy for at least 28 days; minimal clinical evidence of acute GVHD defined as grade 0 to I acute GVHD; minimal evidence of chronic GVHD is defined as mild global score chronic GVHD (as defined by the 2005 NIH consensus project) or no chronic GVHD; subjects with disease that is controlled to stage I acute GVHD or to mild global score chronic GVHD with local topical cutaneous steroids will be eligible for enrollment
Patients with chronic GVHD requiring systemic therapy are eligible
Any active acute GVHD or chronic GVHD greater than grade 1
Patients who have disease relapse, active GVHD or history of more than grade 1 skin acute GVHD, history of chronic (c)GVHD
Clinically diagnosed Grades II to IV acute GvHD as per standard criteria occurring after alloSCT requiring systemic immune suppressive therapy. Biopsy of involved organs with aGvHD is encouraged but not required for study screening.
Active GVHD requiring systemic steroid therapy; medications for GVHD prophylaxis are acceptable
Active chronic GVHD that is extensive
New onset acute GVHD Ann Arbor score 3 following allogeneic bone marrow transplantation (BMT); any clinical severity (Glucksberg grade I-IV) is eligible; patients with prior or existing diagnosis of GVHD without any treatment are eligible; patients given only topical corticosteroids for skin GVHD are eligible
No prior systemic treatment for acute GVHD except for a maximum of 3 days of prednisone (or IV methylprednisolone) ? 2 mg/kg/day; topical skin steroid treatment, non-absorbable oral steroid treatment for gastrointestinal (GI) GVHD, and resumption of GVHD prophylaxis agents (e.g., calcineurin inhibitors) are permissible; patients enrolled in BMT CTN 1501 who randomized to sirolimus are also eligible
Biopsy of acute GVHD target organ is strongly recommended but not required; enrollment should not be delayed for biopsy or pathology results; patients who do not enroll within 3 days of initiation of systemic steroid treatment for acute GVHD are not permitted to participate
Patients with chronic GVHD only; patients diagnosed with overlap syndrome are still eligible
Use of other drugs for the treatment of acute GVHD
Steroid therapy for indications other than GVHD at doses > 0.5 mg/kg/d of methylprednisolone or equivalent within 7 days prior to initiation of GVHD treatment
Active GVHD grade ? 2
Patients with active GVHD > grade 2 will be excluded; patients with recent increase in the immunosuppressive medication dose within last 2 weeks to control GVHD will not be included; patients with grade 1 or lower GVHD on =< 10 mg prednisone without any additional immunosuppressive therapies (tacrolimus, prograf, etc) will be eligible
EXCLUSION CRITERIA FOR ENROLLMENT: Most recent alloHCT performed did not utilize PTCy GVHD prophylaxis
EXCLUSION CRITERIA FOR ENROLLMENT: The use of immunosuppression for grade II-IV acute GVHD within 28 days prior to the infusion of PTCy-MILs
EXCLUSION CRITERIA FOR ADDITIONAL PTCy-MILs INFUSION AT RELAPSE: The presence of active GVHD requiring treatment
Patients with chronic GVHD diagnosed within 3 years after hematopoietic stem cell transplant (HSCT) for any disease, with any graft, and any conditioning regimen with at least one manifestation secondary to fibrosis, including: sclerodermatous skin changes, dry mouth, dry eye, esophageal strictures, or vaginal GVHD
Has received Hematopoietic Stem Cell Transplantation (HSCT) within 60 days of the first dose of DS-3032b, is on immunosuppressive therapy post-HSCT at the time of screening, or has clinically significant GVHD (use of topical steroids for ongoing skin GVHD will be permitted). Subjects must have a washout period of >=2 weeks or at least 4 half-lives from their last systemic immunosuppressive treatment for GVHD.
Patients with active acute GVHD grades II-IV
Allogeneic patients if: i. patients had engrafted donor cells (i.e., > 20% donor T-cell from peripheral blood [PB]/polymerase chain reaction [PCR]); and, ii. patients NOT in complete remission (CR) after their allogeneic transplant, and off tacrolimus and/or mycophenolate mofetil for at least 3 to 4 weeks with no signs of GVHD; or, iii. patients had evidence of relapse after their transplant who are off tacrolimus and/or mycophenolate mofetil or other immunosuppressants for GVHD for 3 to 4 weeks with no signs of GVHD (prednisone doses =< 10 mg are permitted as stated previously)
Active GVHD or recent GVHD and still on > 10 mg prednisone (or equivalent)
Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate
No active acute GvHD >= grade II
No extensive chronic GvHD
Any patient with either progressive aGvHD or steroid refractory (SR) aGvHD after hematopoietic stem cell transplant (HSCT) will be eligible; prophylactic GvHD therapy with cyclosporine, tacrolimus, mycophenolate mofetil (MMF), or sirolimus can be continued; biopsy/pathological confirmation of skin/gastrointestinal or liver GvHD is not required, but it is encouraged
Patients with late onset acute GvHD will be eligible; this includes features of classical acute GvHD without diagnostic or distinctive manifestations of chronic GvHD occurring beyond 100 days of HSCT
Patients with prior history of severe (grade III or IV) acute GVHD even if resolved if post-transplant
Active, acute GvHD > grade II or extensive, chronic GvHD
Active, acute GvHD > grade II or extensive, chronic GvHD
Either no evidence of graft-versus-host disease (GVHD) or minimal clinical evidence of acute GVHD and chronic GVHD while off of systemic immunosuppressive therapy for at least 28 days; minimal clinical evidence of acute GVHD is defined as grade 0 to I acute GVHD; minimal evidence of chronic GVHD is defined as mild global score chronic GVHD (as defined by the 2005 NIH consensus project) or no chronic GVHD; subjects with disease that is controlled to stage I acute GVHD or to mild global score chronic GVHD with local therapy only, e.g., topical cutaneous steroids, will be eligible for enrollment
Anti-GVHD agents posttransplant
Graft failure, acute or extensive chronic GvHD
Patients receiving other investigational drugs for GVHD. Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed
GvHD requiring systemic immunosuppressive therapy
Extensive chronic GvHD requiring ongoing immunosuppression with calcineurin inhibitors
any systemic therapy against GvHD < 2 weeks prior to study Day 1
Ongoing active acute or chronic GVHD requiring immunosuppressive therapy or signs of acute (a)GVHD or chronic (c)GVHD requiring treatment
As GvHD is a clinical diagnosis, and patients will have already been initiated on steroid therapy at the discretion of the attending physician, tissue confirmation of refractory GvHD by biopsy is not required for entry to this study; it is anticipated that most, but not all, patients will have undergone tissue confirmation of the initial diagnosis of GvHD; however lack of tissue confirmation for this clinical syndrome is not exclusionary
Subject has active clinically significant GVHD or is on treatment with systemic corticosteroids for GVHD.
Subject must have no evidence of active acute or chronic GVHD (Grade 0) for 4 weeks prior to the first dose of lenalidomide.
If the subject has a history of maximum Grade 1 or 2 GVHD that was treated with systemic steroid (? 0.5 mg/kg/day prednisone equivalents) or other non-steroid systemic IST, the subject must be off all IST for at least 2 weeks, and must have ceased treatment doses of steroids for GVHD (? 0.5 mg/kg/day prednisone equivalents) for at least 4 weeks. o If the subject has a history of Grade 3 or greater GVHD, the subject must be off all systemic IST for 4 weeks o Topical therapy is permitted and does not imply the subject has active acute or chronic GVHD.
Clinically suspected Grades II to IV acute GVHD as per MAGIC guidelines, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.
Subjects with steroid-refractory acute GVHD, defined as any of the following:
Has received more than 1 systemic treatment in addition to corticosteroids for acute GVHD.
Presence of GVHD overlap syndrome as per NIH guidelines.
Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening
Patients with standard-risk acute GVHD, according to refined Minnesota Criteria. Refined Minnesota Criteria are available at https://redcap.ahc.umn.edu/surveys/?s=bNmFhseJIf. Standard-risk acute GVHD according to the refined Minnesota Risk Criteria requires meeting one of the criteria below:
Acute Minnesota Standard Risk GVHD requiring systemic immune suppressive therapy.
Patients receiving sirolimus (for any indication including GVHD prophylaxis) within 14 days of screening for enrollment.
A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment.
Clinically suspected Grades IIB to IVD acute GVHD as per modified MN-CIBMTR criteria, occurring after allo-HSCT with any conditioning regimen and any anti-GVHD prophylactic program.
Subjects may, but are not required to, have previously received corticosteroids for acute GVHD:
Has progressed on more than 2 prior treatment regimens for acute GVHD.
Requirement for active immunosuppression to treat GVHD
Any drug used for GVHD within 4 weeks prior to enrollment
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
Patients must have a diagnosis of a chronic GVHD according to the National Institute of Health (NIH) Consensus Criteria
Patients must have failed at least one prior line of systemic immune suppressive therapy for management of chronic GVHD
Major surgery within 14 days before enrollment\r\n* Does not include placement of venous access device, bone marrow biopsy, GVHD diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation care
Diagnosis of chronic GVHD according to National Institutes of Health (NIH) Consensus Criteria\r\n* May have either classic chronic GVHD or overlap subtype of chronic GVHD
Failure of at least one prior line of systemic immune suppressive therapy for management of chronic GVHD
Surgery within 21 days prior to enrollment\r\n* Does not include placement of venous access device, bone marrow biopsy, GVHD diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation care
New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment
Patients with acute GVHD grade II-IV
Steroid dependent or refractory classic chronic GVHD disease.
Known or suspected active acute GVHD.
Patients on other experimental protocols for prevention of acute GVHD
No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI
HCT recipients newly requiring systemic glucocorticoid therapy (at >= 1 mg/kg/day prednisone or equivalent) for chronic GVHD\r\n* In the phase I component of the trial, only those with overall moderate or severe global composite score are eligible\r\n* In the phase II component of the trial, patients of any global composite score are eligible, provided they have need for systemic therapy for chronic GVHD
Previous systemic glucocorticoid therapy (at >= 1 mg/kg/day prednisone or equivalent) for chronic GVHD\r\n* Prior systemic glucocorticoid therapy for acute GVHD is permitted\r\n* Prior or ongoing systemic immune suppressive agents (including, but not limited to common examples such as calcineurin inhibitors, sirolimus, mycophenolate mofetil) provided for either prevention or treatment of acute GVHD are permitted and part of routine standard of care\r\n* Patients with progressive, uncontrolled manifestations of acute or chronic GVHD despite >= 1mg/kg/day prednisone (or equivalent) therapy have steroid-refractory disease, and are therefore not eligible for this study
No minimum platelet count is required by this trial, as this is a frequent manifestation of poor-risk chronic GVHD, and such patients may benefit from this protocol therapy
Patients with irreversible damage as the only manifestation of chronic GVHD (irreversible contractures or sicca syndrome)
Patients with uncontrolled acute or chronic GVHD or refractory disease not responding to conventional therapy
Patients with active acute GVHD who have been initiated on therapy or had therapy escalation within 21 days are not eligible
Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD, or who are less than 100 days from stem cell infusion
Patients with any NIH subtype (classic or overlap) of chronic GVHD who are starting treatment with ECP
Stage 4 gastrointestinal GVHD as per Seattle-Glucksberg criteria
Suitable candidates are patients with classic chronic GVHD or overlap syndrome (classic chronic plus acute GVHD)that is: a)Previously untreated (newly diagnosed) as defined by having received < 14 days of prednisone (or equivalent) before enrollment/randomization to study therapy; b)Previously treated but inadequately responding after ? 16 weeks of initial therapy with prednisone and/or calcineurin inhibitor (CNI) ± additional non-sirolimus agent (started at the time of chronic GVHD diagnosis).
Patients with late persistent acute GVHD or recurrent acute GVHD only.
Receiving sirolimus for treatment of chronic GVHD (sirolimus for prophylaxis or treatment of acute GVHD is acceptable).
Receiving therapy for chronic GVHD for more than 16 weeks.
Current grade II to IV acute GVHD or extensive chronic GVHD
Presence of chronic GvHD at Screening (including acute-chronic overlap syndrome).
Hyperacute GvHD defined as onset of GvHD within the first 15 days following hematopoietic stem cell infusion.
Received systemic agents other than corticosteroids for treatment of acute GvHD. GvHD prophylaxis agents (example, calcineurin inhibitors) may be continued.
Subjects with Stage 1-4 (per the Modified Keystone Grading Schema) acute GVHD of the lower GI tract, without signs of chronic GVHD, at the time of diagnosis, which developed in the first 180 days following allogeneic hematopoietic cell transplantation (HCT) using bone marrow, peripheral blood, or cord blood; or after preplanned donor lymphocyte infusion.
Stage of acute GVHD of the lower GI tract will be determined using the Modified Keystone Grading Schema.
Subjects with signs and symptoms of chronic GVHD.
Subjects who received previous systemic treatment for acute GVHD, except for a maximum of 3 days (72 hours) of 2 mg/kg corticosteroid therapy.
Active grades III or IV acute GVHD
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
GVHD therapies: Any drug used for GVHD within 4 weeks prior to leukapheresis
Participant with manifestations of chronic GvHD
Participant with acute/chronic GvHD overlap syndrome
Participant receiving GvHD treatment other than continued prophylaxis (eg, cyclosporine and/or mycophenolate mofetil, etc) or corticosteroid therapy. In addition, a participant who received the first dose of corticosteroid therapy for acute GvHD with lower GI involvement more than 72 hours before the first dose of study treatment is not eligible for the study
Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
Symptomatic moderate or severe chronic GVHD patients in need of a change of systemic immunosuppressant (IS) therapy
GVHD\r\n* ARM A: Without evidence of active or prior history of GVHD\r\n* ARM B: Patients with active GVHD, or with GVHD controlled by steroids or other immunosuppressive medications
Phototherapy-unless administered for acute GVHD
Patient was diagnosed with Grade B-D acute GVHD requiring corticosteroid systemic therapy. The subject may have Grade C or D aGVHD involving the skin, liver, and/or gastrointestinal (GI) tract or may have Grade B aGVHD involving the liver and/or GI tract, with or without concomitant skin disease. Acute GVHD is defined as the presence of skin rash and/or persistent nausea, vomiting, and/or diarrhea and/or cholestasis presenting in a context in which aGVHD is likely to occur and where other etiologies such as drug rash, enteric infection, or hepatotoxic syndromes are unlikely or have been ruled out.
Patient has received systemic agents other than steroids and prophylactic agents for primary treatment of acute GVHD.
Active GVHD
GVHD: Patients will not be eligible for DLI if they have grades 2 – 4 acute GVHD or extensive chronic GVHD
Planned administration of alemtuzumab (Campath-1H) or other investigational agents as alternative agent for GVHD prophylaxis
Diagnosis and staging of de novo acute GvHD of the GIT (any site except isolated “upper” GIT disease);\r\n* Patients must be classifief as \high risk\ by the combined Minnesota (MN)/Center for International Blood and Marrow Transplant (CIBMTR) grading\r\n* Biopsies should be obtained by full endoscopy including esophagogastroduodenoscopy (EGD) and flexible sigmoidoscopy or colonoscopy; however, it is not necessary to have confirmation of GvHD diagnosis before initiating IASA therapy; such is not recommended\r\n* If other diagnoses are excluded, it is not necessary to biopsy all potentially involved sites in the GIT to initiate therapy\r\n* It is possible that other diagnoses may be present as well, and this should not exclude eligibility so long as they are distinct (this statement is generic, but applies especially to various types of infective colitis; that said, concomitant anti-infective therapy must be on-going)\r\n* Although this study is designed for patient with high-risk de novo, acute GvHD of the lower gastrointestinal tract, selected patients with more advanced, even “steroid refractory” acute GvHD may be considered for this study providing they fulfill two criteria: 1) have no history of prior IASA; and 2) are personally approved by the principal investigator (PI), or in his absence, his designee
Prior or on-going therapy:\r\n* No previous systemic (topical allowed) therapy for acute GvHD --except for a maximum (and ideally less) of 48 hours of prior glucocorticoid (GC) therapy, > 0.5 mg/kg/day of MePDSL or equivalent after the onset of acute GvHD\r\n* An exception to the above exists for patients with prior acute GvHD (of any site) who received GC therapy, experienced a complete response (CR), were tapered off GC and recurred >= 15 days later; such are eligible after review by the PI or his designee\r\n* For patients with SR, no prior stipulations – beyond prior IASA – will be specified\r\n* The use of on-going acute GvHD prophylaxis will be continued as above (if in the rare case this is not possible due to toxicity, discussion with, and approval by the study PI is required)\r\n* Moreover, the use of any other IST is allowed if acute GvHD of the GIT develops while the patient is off all IST; IST may be restarted at the discretion of the attending physician after discussion with the PI of this study\r\n* Treatment with oral budesonide is to be started or continued at full dose\r\n* Please consult with the study PI regarding any questions or concerns of study eligibility
Patients may not be receiving any other drugs for the treatment of GvHD or investigational agents, except for a maximum of 48 hours of prior GC therapy, as above (obviously, this requirement is waived for SA – acute GvHD patients; in this case, no requirements are mandated)
Active uncontrolled stage 3-4 acute gastrointestinal (GI) GVHD prior to administration of ibrutinib
Active uncontrolled stage 4 acute liver GVHD prior to administration of ibrutinib
Use of second line systemic therapy for treatment of acute GVHD prior to administration of ibrutinib
Evidence of GVHD at the time of enrollment as assessed clinically
New chronic GVHD therapies (e.g. gleevec, extracorporeal photopheresis, rituximab, immunosuppressive medications) in the 4 weeks prior
Patients receiving other investigational drugs for GVHD; co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed
Participants must have acute GVHD as defined by the clinical impression of the treating physician; biopsy of the involved tissue, while encouraged, is not required for study entry; eligibility includes:\r\n* Acute GVHD developing after allogeneic hematopoietic stem cell transplantation using bone marrow, peripheral blood stem cells, or umbilical cord blood; recipients of non-myeloablative, reduced intensity and myeloablative transplants are eligible\r\n* Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible\r\n* There is no specified time window after day 0 of transplant as acute GVHD is only defined by clinical manifestations\r\n* Patients must have experienced neutrophil engraftment after hematopoietic cell transplant (HCT) as defined by absolute neutrophil counts >= 500/ul x 3 consecutive measurements
Patients with the entity of acute/chronic GVHD overlap syndromes
Participants may not have received > 1 systemic immunosuppressive agent beyond corticosteroids for the treatment of GVHD; GVHD prophylaxis regimens used for an individual patient do not count as additional agents
Patients with steroid (or immunosuppressive therapy [IST]) refractory acute GVHD (aGVHD) or chronic GVHD (cGVHD)
Stable dose of corticosteroids for treatment of GVHD for 2 weeks prior to enrollment (fluctuation of corticosteroids for treatment of anything other than GVHD acceptable)
Participation in an investigational study that has acute GVHD as the primary endpoint
Patients receiving calcineurin inhibitors as part of GVHD prophylaxis
Patients with acute GVHD grades II-IV developing despite GVHD prophylaxis
Patients who have received any systemic agents in addition to steroids for treatment of GVHD
Patients with manifestations of classic chronic GVHD
Patients with acute/chronic GVHD overlap syndrome
Subject has moderate or severe overlap chronic (c)GVHD according to National Institutes of Health (NIH) criteria
Active cGVHD despite treatment with at least two immunosuppressive treatments (not including GVHD prophylaxis) in the past year
FOR THE 31 SUBJECTS ENROLLED IN YEAR 1: If patients are on immunosuppressive therapy for treatment of GVHD, then only those on stable doses for at least 4 weeks (or on tapering doses) will be eligible
Participation in a clinical trial evaluating another preventative strategy for chronic graft-versus-host disease (GVHD), or ongoing participation in a clinical trial for therapy of acute GVHD; prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used > 30 days prior to enrollment
Any evidence of ongoing gastrointestinal or hepatic acute GVHD, or evidence of greater than ongoing stage I cutaneous acute GVHD; ongoing, tapering therapy for resolved acute GVHD is permissible
Any evidence of prior active or resolved chronic GVHD
Patients with Acute GVHD Grade III-IV
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Active and uncontrolled acute GVHD grades III or IV
EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Use of secondary therapy for acute GVHD at any time (defined as any systemic therapy intended to treat acute GVHD besides corticosteroids)
Myeloid or lymphoid hematologic malignancy treated with a reduced intensity (RI) or non-myeloablative (NMA) conditioning HSCT who received calcineurin inhibitor based drug (for example: tacrolimus or cyclosporin) and methotrexate as part of their initial GVHD prophylaxis; patients who received sirolimus as part of their GVHD prophylaxis will be eligible
Active acute or chronic GVHD
Patients actively enrolled on any other GVHD prevention trial
Patients without cGVHD are defined as having no signs or symptoms of GVHD with chronic features diagnosed at any time prior to enrollment
Participation in a clinical trial evaluating another preventative or treatment strategy for chronic GVHD or ongoing participation in a clinical trial for therapy of acute GVHD; prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used > 30 days prior to enrollment
Any evidence of ongoing gastrointestinal or hepatic acute GVHD or evidence of greater than ongoing stage I cutaneous acute GVHD at time of enrollment; ongoing, tapering therapy for resolved acute GVHD is permissible
Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis
Participation in an investigational study that has acute GVHD as the primary endpoint
Subjects receiving pre-transplant conditioning/GVHD prophylaxis regimens other than those defined, herein.
Use of antibiotics to treat chronic infections within 28 days prior to first dose
Active systemic infections requiring antibiotics
Repeated infections requiring oral or i.v. antibiotics
Active or fungal infections requiring systemic treatment within 7 days prior to screening
Acute or chronic infections requiring systemic therapy, including, among others:
Has an active infection requiring systemic therapy (apart from cutaneous infections).
Systemic infection requiring chronic maintenance or suppressive therapy
Significant acute or chronic infections requiring systemic therapy
Documented infections or oral temperature > 38.2 degree Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance therapy; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
No active infections requiring systemic antibiotics
Known active infections or oral temperature > 38.2 Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance or suppressive therapy
Active infections requiring therapy, including HIV, hepatitis
Histry of significant chronic or recurrent infections requiring treatment
Acute or chronic infections requiring systemic therapy, including, among others:
Has an active infection requiring systemic therapy or history of repeated infections
Systemic infection requiring chronic maintenance or suppressive therapy
Serious, active infections requiring treatment with IV antibiotics
Acute infections requiring parenteral therapy
Patients with known systemic infections requiring antibiotics or chronic maintenance/suppressive therapy
Patients with systemic infections requiring active therapy within 72 hours of lymphodepletion
Patients with active systemic infections requiring antibiotics or active hepatitis A, B, or C.
No active infections requiring systemic therapy
Infections or intercurrent illness requiring active therapy
Patients who have active infections requiring therapy.
Patients with active infections requiring systemic treatment.
Active infections requiring systemic antibiotics.
Active infections requiring systemic antibiotics.
certain heart problems, active or chronic infections, serious significant diseases, AIHA requiring treatment, other current cancer or within last 5 years
Active infection requiring systemic treatment or any uncontrolled infections =< 14 days prior to enrollment
Active infections prior to receiving study treatment or systemic infection requiring chronic maintenance or suppressive therapy
Active or chronic recurrent systemic infections that require continuous antimicrobial therapy during the Kevetrin study period
Active infections requiring antibiotics
Patients with systemic infections requiring antibiotics or chronic maintenance/suppressive therapy
Chronic or current active infections requiring systemic antibiotics, antifungals or antiviral therapy
Patients with active systemic infections requiring antibiotics or chronic maintenance/suppressive therapy; once the infection in question has resolved and patient is off antimicrobial treatment, patients may participate
Active infections requiring systemic therapy
Subject has known or suspected HIV or other active infections requiring acute or chronic treatment with systemic antibiotics. Conditions requiring topical antibiotics are acceptable.
Active, uncontrolled infections within 7 days of study entry requiring systemic therapy.
History of iron overload
Clinically significant anemia due to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding. If marrow stain for iron is not available, the transferrin saturation (iron/total iron binding capacity Fe/TIBC) must be >20% or serum ferritin must be >100 ng/dL.
Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology
Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be >= 20% or a serum ferritin >= 100 ng/100 mL or soluble transferring receptor < 5 mg/L.
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Ongoing clinically significant anemia due to factors such as known iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding
Clinically significant iron metabolism disorders (eg, sickle cell anemia)
Use of iron chelators
Have sickle cell disease (confirmed by Hb electrophoresis or more specific tests) or other conditions with iron overload from repeated blood transfusions (see exclusion criteria for exceptions);
Clinically significant anemia according to investigator's assessment due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding.
IMAGING CORRELATIVE STUDY: Patients will be eligible to participate in the FMX imaging study if the participating study center offers this test and they do not meet any of the following criteria:\r\n* Evidence of iron overload as determined by:\r\n** Fasting transferrin saturation of > 45% and/or\r\n** Serum ferritin levels > 1000 ng/ml\r\n* A history of allergic reactions to any of the following:\r\n** Compounds similar to ferumoxytol or any of its components as described in full prescribing information for ferumoxytol injection\r\n** Any IV iron replacement product (e.g. parenteral iron, dextran, iron-dextran, or parenteral iron polysaccharide preparations)\r\n** Multiple drugs\r\n* Unable to undergo MRI or for whom MRI is otherwise contraindicated (e.g. presence of errant metal, cardiac pacemakers, pain pumps or other MRI incompatible devices; or history claustrophobia or anxiety related to undergoing MRI)
Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal bleeding.
Patients must not have documented iron deficiency; all patients must have documented marrow iron stores; if marrow iron stain is not available, the transferrin saturation must be > 20% or a serum ferritin > 100 ng/mL
Patients must not have clinically significant anemia resulting from iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding
Adequate iron stores, defined as transferrin saturation greater than 20 percent (%) and serum ferritin greater than 400 nanogram per Milliliter (ng/mL), measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain
Known allergy to iron dextran or presence of human anti-mouse antibodies
Subjects must have liver iron value of < 15 mg/g/dry weight; iron quantitation may be performed by imaging such as T2*magnetic resonance imaging (MRI) or by biopsy
PART I: History of iron overload or hemochromatosis
PART II: History of iron overload or hemochromatosis
Any other evidence of severe iron overload that, in the Investigator's opinion, warrants exclusion.
DONOR: Anemia (Hb < 11 gm/dl) or thrombocytopenia (platelets < 100,000 per ul); however, potential donors with Hb levels < 11 gm/dl that is due to iron deficiency will be eligible as long as the donor is initiated on iron replacement therapy and the case is individually approved by National Institutes of Health (NIH) Blood Bank
Patients requiring iron supplementation will be excluded
Evidence of iron deficiency anemia including, hemoglobin (Hgb) < 11 g/dL, but > 8 g/dL; and transferrin saturation (TSAT) < 20%
Any anemia treatment within 4 weeks before inclusion (oral iron, IV iron, or erythropoiesis-stimulating agents), or transfusion of packed red blood cells (PRBCs) in 2 weeks
Hemochromatosis or other iron storage disorders
Subjects with anemia (defined as a hemoglobin < 12) who have a ferritin < 40 ng/mL and iron percentage of saturation (% sat) < 20%
Has history of iron overload
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations; subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Subjects with known hypersensitivity and allergy to iron
Subjects with evidence of iron overload with a pre-study ferritin level greater than 370 ng/ml and percent saturation of transferrin level greater than 40%; patients with lab values above these limits may be included in the study if documented hematology consultation rules out hemochromatosis, idiopathic or iatrogenic iron overload
Patients with evidence of iron overload, hemosiderosis/hemochromatosis will be excluded for the bone sarcoma study; however, they can undergo MRI exam without ferumoxytol enhancement for the ON study
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known iron overload (genetic hemochromatosis); in subjects with a family history of hemochromatosis, hemochromatosis must be ruled out prior to study entry with normal values of the following blood tests: transferrin saturation (TS) test and serum ferritin (SF) test; all associated costs will be paid by the study
Participants with concurrent clinical diagnosis, evidence of suspected hemochromatosis, or other diseases of iron metabolism (i.e., iron overload)
Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)
Subjects with concurrent clinical diagnosis of evidence of active iron overload defined by the following 1) ferritin >= 250 ng/mL in men or >= 200 ng/mL in women AND 2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as percent, >= 45%
Subjects with evidence of iron overload
Participants with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations, are not eligible; participants with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator’s discretion
Participants that have a known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)
Subjects who have a known allergy to iron
Subjects with sickle cell disease, hemoglobinopathy, hemochromatosis or other clinical conditions that may lead to iron overload
No other known etiology of the thrombocytopenia (such as infection, medication, etc.) or anemia (such as blood loss, iron deficiency, etc.).
Primary or secondary iron overload
Clinically documented or risk of primary or secondary iron overloading (e.g. history of thalassemia, sickle cell anemia, hereditary hemochromatosis, multiple transfusions with any reason), anemia not caused by iron deficiency
Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator’s Drug Brochure, 2012); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator’s discretion
Subjects with known or suspected iron overload (genetic hemochromatosis or history of multiple transfusions)
Iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology
Subject has intolerance or hypersensitivity to iron or dextran compounds or to SiennaXP.
Subject has an iron overload disease.
Serum iron, total iron binding capacity, and serum ferritin within normal institutional limits; patients are eligible even if they are taking an iron supplement
Receipt of any other iron-oxide based nanoparticle therapy or IV iron within 4 weeks of scans
A known diagnosis of hemochromatosis, mitochondrial disorder, or iron overload
Biliary tract carcinoma.
Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions
Has an active infection requiring systemic therapy within 3 days of registration (NOTE: except for uncomplicated urinary tract infection [UTI])
Intraoperative frozen section suggesting hepatobiliary, pancreatic, adrenal, or urinary tract cancer
Patients with active infection requiring antibiotics are not eligible (with the exception of uncomplicated UTI and uncomplicated respiratory tract infections)
Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
Patients who have an active infection requiring systemic therapy are not eligible, except for uncomplicated urinary tract infections
The patient has any ongoing or active infection, including active tuberculosis; Note: a urinary tract infection controlled with oral antibiotics initiated at least 7 days prior to study entry is acceptable
Acute urinary tract infection.
Lower urinary tract symptoms defined by International Prostate symptom score (IPSS) > 20
Carcinoma in situ (CIS) in the past in the urinary tract.
Known untreated or uncontrolled acute infection, including urinary tract infection, within 7 days of study entry
Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
Active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection)
Have known urinary outflow obstruction, or inflammation of the urinary bladder (cystitis).
No characteristics suggesting a potential higher risk of infection with intraprostatic injections:\r\n* Recurrent urinary tract infections or history of prostatitis within 3 months prior to enrollment into the study\r\n* Urine analysis positive for nitrites and leucocyte esterase; such patients could be considered for the study after treatment and resolution of the infection\r\n* Active proctitis\r\n* History of prostatic abscess\r\n* Taking immunosuppressive medication including systemic corticosteroids\r\n* Active hematologic malignancy
CHEMOTHERAPY/CELL INFUSION ELIGIBILITY: Urinalysis within 14 days demonstrating that no urinary tract infection is present
Urinary tract obstruction or marked hydronephrosis
Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
PHASE I: Patients should be free of active infection requiring antibiotic therapy (except for uncomplicated urinary tract infections)
PHASE II: Patients should be free of active infection requiring antibiotic therapy (except for uncomplicated urinary tract infections)
Current severe urinary incontinence, hydronephrosis, severe voiding dysfunction, any level of urinary obstruction requiring indwelling/condom catheters
All types of urinary diversions
Has an active infection requiring systemic therapy with the exception of an uncomplicated urinary tract infection
Active urinary tract infection
Urinary tract or rectal fistula
Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
Urinalysis within 14 days demonstrating no evidence of a urinary tract infection
Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily treated, patients can enter the study)
Known urinary tract obstruction
History of recurrent severe urinary tract infections (UTIs) per investigator judgment. Subjects with a current UTI requiring antibiotic treatment may defer the initiation of Vicinium treatment on Day 1 until resolution of the UTI (even if this extends the screening period requirements to start of Vicinium treatment).
Acute unresolved Urinary Tract Infection (UTI)
Patients should be free of active infection requiring antibiotics (with the exception of an uncomplicated urinary tract infection [UTI])
Patients must have high grade upper tract urothelial carcinoma proven by one of the following:\r\n* Biopsy;\r\n* Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional imaging; or\r\n* Urinary cytology and a mass visualized during upper urinary tract endoscopy
Urinary tract infection, including particularly bladder infection, must be resolved prior to being placed on study
Uncontrolled infection, fever > 100 degrees F; or antibiotic therapy < 72 hours prior to registration; or urinary tract infection < 72 hours prior to registration
active urinary tract infection;
urinary tract or rectal fistula;
Recent infection requiring a course of systemic anti-infectives that was completed =< 14 days prior to enrollment (exception can be made at the judgment of the PI for oral treatment of an uncomplicated urinary tract infection [UTI])
Patients must be free of active infections requiring antibiotics, with the exception of uncomplicated urinary tract infections (UTIs)
Prior or concomitant urothelial tumors of the upper urinary tract or urethra
Untreated urinary-tract infection
Upper urinary tract disease (eg, vesicoureteral reflux or urinary-tract stones) that would make multiple transurethral procedures a risk
Concurrent febrile illness, urinary tract infection, or gross hematuria
Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
No active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection)
Active urinary tract infection
Clinically important genital/urinary tract dysfunction
Presence of an acute infection requiring antibiotics within 4 weeks of study entry or a chronic infection including but not limited to: urinary tract infection, HIV, viral hepatitis
Have an active urinary tract infection (UTI),
Have vaginal dryness, dyspareunia, or >= 3 urinary tract infections per year since starting AI therapy
Subjects with current or suspected urinary tract or bladder infection(s);
Patients with active urinary tract infections
Patient has systemic infection or evidence of any surgical site infection (superficial or organ space), including active urinary tract infection
Patients who have upper tract TCC
Documented acute prostatitis or urinary tract infections
Urine culture positive for significant urinary tract infection (UTI)
Patient has systemic infection or evidence of any surgical site infection (superficial or organ space), including active urinary tract infection
Current, clinically significant, active infection that in the opinion of the Investigator would make them an unfit participant in the trial
Clinically significant active infection, in the judgment of the investigator
Clinically significant active infection or uncontrolled medical condition
Has a clinically significant active infection requiring systemic therapy.
clinically significant active infection
Has any clinically significant infection
Any significant systemic infection within 4 weeks prior to dosing
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
Active clinically significant infection requiring antibiotics
Must not have known active or clinically significant hepatitis A, B or C infection.
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
Active clinically significant uncontrolled infection
Evidence of active tuberculosis or recent clinically-significant infection requiring systemic therapy.
Active clinically significant infection
Active clinically significant infection within 7-days of study treatment.
No evidence of clinically significant active infection and no serious infection within the past month
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals
Any clinically significant active infection that requires systemic treatment at the time of enrollment
Evidence of active tuberculosis or recent (<1 week prior to first scheduled dosing) clinically significant infection requiring systemic therapy.
Clinically significant active infection (e.g. tuberculosis, viral hepatitis, HIV)
Active clinically significant infection requiring antibiotics
Active and clinically significant systemic or localized infection.
Other significant active infection.
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals. The Medical Monitor should be contacted for any uncertainties.
Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals, or anti-fungals.
Other significant active infection.
No evidence of a clinically significant active infection
Active clinically significant uncontrolled infection
Active clinically significant uncontrolled infection
Active clinically significant infection
Clinically significant active infection
Active infection requiring parenteral or oral antibiotics within 2 weeks before planned start of study therapy
Known active infection requiring parenteral or oral anti-infective treatment within 14 days of randomization.
Current infection requiring parenteral antibiotics
Known active infection requiring parenteral or oral anti-infective treatment, once a patient has completed antibiotics and symptoms of infection have resolved to < grade 2, they are then considered eligible from an infection standpoint
Active infection requiring parenteral antibiotics within 2 weeks before planned first dose of study drug
Serious/active infection or infection requiring parenteral antibiotics
Current infection requiring parenteral antibiotics
Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy
Current infection requiring parenteral antibiotics
Have uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics.
Known active infection requiring parenteral anti-infective treatment at the time of initiation of treatment
Active infection requiring parenteral antibiotics
Serious/active infection or infection requiring parenteral antibiotics
Patients with acute hepatitis or active infection that requires parenteral antibiotics
Active infection requiring parenteral antibiotics
Subjects with active infection that requires parenteral antibiotics
Active infection requiring parenteral antibiotics
Active infection requiring parenteral antibiotics
Major active infection requiring parenteral antibiotics.
Active infection requiring parenteral antibiotics
Active infection requiring parenteral antibiotics.
Patients must not have an active infection requiring current treatment with parenteral antibiotics
Patients with acute hepatitis or active infection that requires parenteral antibiotics
Patients should be free of active infection requiring parenteral antibiotics.
Patients with active infection requiring parenteral antibiotics.
Known active infection requiring parenteral or oral anti-infective treatment
Ongoing infection that requires parenteral treatment with antibiotics
Current infection requiring parenteral antibiotics
Patients should be free of active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry.
Subjects with active infection that requires parenteral antibiotics
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 1
Known active infection requiring parenteral or oral anti-infective treatment
Serious/active infection or infection requiring parenteral antibiotics
Patients with acute hepatitis or active infection that requires parenteral antibiotics are excluded
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 1
Patients with acute hepatitis or active infection that requires parenteral antibiotics.
Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics
Known active infection requiring parenteral or oral anti-infective treatment.
Ongoing or active infection requiring parenteral antibiotics.
Serious/active infection or infection requiring parenteral antibiotics
Active infection requiring parenteral antibiotics
The patient has ongoing or active infection requiring parenteral antibiotics.
Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 1 week prior to first study drug administration.
Serious infection requiring parenteral antibiotics within 14 days of enrollment
Patients with any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first study drug administration.
Serious/active infection or infection requiring parenteral antibiotics
Active infection requiring parenteral antibiotics within one-week prior to study
Active infection requiring parenteral antibiotics
Have had an infection requiring the use of parenteral antibiotics within 14 days prior to the start of Day 1;
Any infection requiring parenteral antibiotics within the past 2 weeks
No active infection within 14 days of study enrollment requiring parenteral antibiotics
Known active infection requiring parenteral or oral anti-infective treatment within defined period
Current infection requiring parenteral antibiotics