Any corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization.
Chronic use, as defined by > 2 weeks of a corticosteroid agent that is >= 20 mg/day of prednisone or its equivalent, within 4 weeks prior to first administration of BI
Participants who received greater than 10 days of corticosteroids in the preceding 30 days prior to enrollment; physiologic dosing of steroid is 4-5 mg/m^2/day prednisone, 0.03-0.15 mg/kg/day dexamethasone, or 0.5-0.75 mg/kg/day hydrocortisone; contact the AMC Protocol Team for physiologic dosing limits for other corticosteroids
Subjects requiring systemic steroid therapy should be receiving ? 10 mg/day of prednisone (or equivalent) for the 2 weeks preceding start of study.
Subject with Graft vs. Host Disease (GVHD) who is receiving treatment with systemic glucocorticoids > 10 mg/day equivalent of prednisone; however, treatment with low dose glucocorticoids (? 10 mg/day equivalent of prednisone) is permitted
Participants must have steroid refractory cGVHD, defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at >= 0. 5 mg/kg/day (or equivalent) for at least 4 weeks; patients may remain on steroids while enrolled in the study
FOR THE PHASE II PORTION OF THE STUDY: Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms; patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible
Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
Use of systemic corticosteroids >0.5 mg/kg/day within 10 days prior to obtaining 200 mL whole blood starting material.
A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week, OR
Disease persistence without improvement despite continued treatment with prednisone at > 0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks, OR
Increase to prednisolone dose to > 0.25 mg/kg/day after 2 unsuccessful attempts to taper the dose
Any corticosteroid therapy for indications other than cGvHD at doses > 1 mg/kg/day methylprednisolone or equivalent within 7 days of Cycle 1 Day 1
EXCLUSION - INFUSION: Current use of systemic corticosteroids > 0.5 mg/kg/day
Systemic glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last 4 weeks prior to first dose, unless tapered and on a stable dose (prednisone ?10 mg/day orally or equivalent) for at least 1 week.
Patient must be asymptomatic at time of getting SRS (day 0) on trial; prednisone < 10mg/day for at least 7 days prior to treatment is allowed
Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to cycle 1 day 1
Use of systemic corticosteroids > 0.5 mg/kg/day prednisolone or equivalent does of alternative corticosteroid within 10 days prior to obtaining 200 mL starting material
Doses ? 10 mg/kg/day prednisolone or equivalent is allowed, provided that the steroid dose has been stable or tapering for at least 14 days prior to the first dose of CUDC-907.
The patient is receiving immunosuppressive therapy for prophylaxis following a prior organ transplant (solid organ or allogeneic stem cell) or management of immune-mediated toxicities due to immunotherapy. Low-dose corticosteroid (defined as < 10mg/day of prednisone or equivalent) therapy is permitted.
Currently taking corticosteroids (> 0.5 mg/kg/day prednisone or equivalent)
Currently taking corticosteroids (> 0.5 mg/kg/day prednisone or equivalent)
Subjects who received any corticosteroid therapy (for non-GVHD) at doses >0.5 mg/kg/day prednisone (or equivalent) within 7 days prior to the onset of GVHD therapy.
Patients may not be receiving systemic corticosteroid therapy at a prednisone dose > 20 mg/day (or steroid equivalent) within 2 weeks of starting study.
Must have one of the following diagnoses:\r\n* Acute GVHD (grade II-IV) requiring systemic therapy and refractory/unresponsive to glucocorticoid (>= 1 mg prednisone-equivalent/kg x 1 week)\r\n* Chronic GVHD that is extensive and not improved despite therapy with glucocorticoid (>= 0.5 mg prednisone-equivalent/kg/day) and therapeutic doses of a calcineurin inhibitor for at least 4 weeks, or worsened within 2 weeks, or overlap syndrome not responding to glucocorticoid treatment (>= 1 mg prednisone-equivalent/kg x 1 week)
Corticosteroid therapy at the time the patient enters the protocol; NOTE: patients using prednisone or its equivalent for adrenal failure or using =< 10mg of prednisone/day for other benign causes are accepted
Current use of systemic corticosteroids > 0.5 mg/kg/day
Currently taking corticosteroids (> 0.5 mg/kg/day prednisone or equivalent) for therapy of GVHD
TREATMENT WITH SJCAR19: Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to CAR T-cell infusion
History of any condition requiring anti-platelet therapy (aspirin > 300 mg/day, clopidogrel > 75 mg/day)
Chronic steroid therapy, however prednisone or its equivalent is allowed at =< 10 mg/day.
Inability to begin a prednisone dose ?0.5 mg/kg/d for the treatment of cGVHD
The following medications are prohibited within 2 weeks of enrollment and while on study drug:\r\n* 5 alpha-reductase inhibitors (finasteride, dutasteride)\r\n* Biologic or other agents with anti-tumor activity against prostate cancer (excluding herbal supplements)\r\n* Systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone\r\n** Premedication with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone is permitted prior to docetaxel infusions\r\n* Androgens (testosterone, dehydroepiandrosterone [DHEA], etc.)
Patients on corticosteroids > 0.1 mg/Kg/day (i.e. > the maximum dose of 4mg/day)
Subjects who are currently using more than 5mg/day of prednisone (or an equivalent glucocorticoid exceeding physiologic replacement levels)
The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent
Chronic steroid dependency (prednisone equivalent > 10 mg/day); any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment
Has undergone RIC allo BMT: cyclophosphamide (14.5 mg/kg/day) days ?6 and ?5, fludarabine (30 mg/m/day) days ?6 through ?2, total body irradiation (200 cGy) day ?1, day 0 infusion of an unmanipulated bone marrow graft (target 4.0 x 10^8 nucleated cells/kg recipient ideal body\r\nweight), cyclophosphamide (50 mg/kg) days +3 and +4, mycophenolate mofetil days +5 through +35, tacrolimus or sirolimus days +5 through days +180 based on protocol, and filgrastim (5 mcg/kg/day) day +5 through neutrophil recovery (> 1000/uLiter) following Hopkins BMT policy\r\nmanual guidelines
Corticosteroid use >30 mg/day of prednisone or equivalent, for purposes other than lymphoma symptom control
Corticosteroid therapy (>10 mg prednisone/day or equivalent) within 1 week prior to the first dose of study drug
Participants must have steroid-refractory cGVHD, which is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at 0.20 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms
Confirmed diagnosis of steroid refractory aGvHD defined as patients administered high-dose systemic corticosteroids (methylprednisolone 2 mg/kg/day [or equivalent prednisone dose 2.5 mg/kg/day]), given alone or combined with calcineurin inhibitors (CNI) and either:
Requirement for an increase in the corticosteroid dose to methylprednisolone ?2 mg/kg/day (or equivalent prednisone dose ?2.5 mg/kg/day) , OR
Failure to taper the methylprednisolone dose to <0.5 mg/kg/day (or equivalent prednisone dose <0.6 mg/kg/day) for a minimum 7 days.
Clinically significant and ongoing immune suppression including, but not limited to: systemic immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of 0.5 mg prednisone/kg per day, or higher), chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection
Concurrent systemic steroid therapy higher than physiologic dose (> 7.5 mg/day of prednisone or equivalent)
Patients who are on high dose steroid (equivalent of prednisone more than 10 mg a day) or immune suppression medications
Patients must be on single immune suppression therapy with either tacrolimus or cyclosporine at the time of CD8+ memory T-cell infusion; prednisone at a physiologic dose of 5 mg per day or less is allowed
If on corticosteroids, a dose of < 1 mg/kg prednisone per day or equivalent that has been stable for ? 21 days prior to the first dose of PRTX-100. High-dose pulse steroid therapy is NOT allowed within 14 days prior to the first dose of PRTX-100.
Patients must be clinically stable and off or on low-dose (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) corticosteroid for at least one week prior to study registration
Failure to respond to corticosteroids, defined as:\r\n* Progression of chronic GVHD despite optimal first line therapy (> 0.5 mg/kg/day of prednisone dose equivalent [PDE] for two weeks) or\r\n* No improvement after 4-8 weeks of sustained therapy; sustained therapy should include 2 weeks of > 0.5 mg/kg/day of PDE or\r\n* Inability to taper steroid dosage to less than 0.5 mg/kg/day of PDE without worsening of chronic GVHD or \r\n* Need for second or third line therapy beyond corticosteroids and calcineurin inhibitors or sirolimus, irrespective of other criteria
Patients requiring high doses of glucocorticosteroids (? 0.3 mg/kg prednisone or its equivalent)
Patient is on chronic systemic steroid therapy (> 10 mg/kg prednisone or equivalent) within two weeks before the planned date for first dose randomized treatment or on any other form of immunosuppressive medication (premedication with corticosteroid for nausea is permitted)
Chronic usage of aspirin greater than 81 mg/day
Primary immunodeficiency and need for chronic steroid therapy, however prednisone is allowed at < 10 mg/day (Turnstile I)
Patients must be clinically stable and off or on low-dose (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) corticosteroid for at least one week prior to study registration
Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents; patients must be on no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone for at least one week before study registration; topical corticosteroids are acceptable
Current use of systemic corticosteroids > 0.5 mg/kg/day
Patients must be clinically stable and off or on low-dose (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) corticosteroid for at least one week prior to study registration
Underwent Autologous SCT 60-120 days prior to registration including:\r\n* BEAM conditioning (BCNU: 300 mg/m2 IV day -7, Etoposide: 100 mg/m2 IV BID days -6,-5,-4,-3, Cytarabine: 100 mg/m2 IV BID days -6,-5,-4,-3, Melphalan: 140 mg/m2 IV day -2)\r\n* Minimum of 2 x 10^6 CD34+ cells/kg infused
Patients must have clinical aGvHD and pathologic findings consistent with the diagnosis by biopsy of at least 1 involved site and treated initially with steroids at prednisone-equivalent doses ?1 mg/kg/day, and i) worsening of GvHD manifestations across any interval of at least 2 days before tapering of steroid doses has begun, or ii) persistence of grade II to IV aGvHD across any interval of at least 7 days without improvement during steroid treatment at any prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with contraindication to continued treatment at higher steroid doses because of severe steroid-related toxicity (e.g., myopathy), or iii) initial response of GvHD manifestations followed by exacerbation of aGvHD across any interval of at least 3 days while tapering glucocorticoid treatment at any prednisone-equivalent dose >0.4 mg/kg/day or at any lower dose in patients with contraindication to continued treatment at higher steroid doses because of severe steroid-related toxicity (e.g., myopathy).
Ability to be off prednisone and other immunosuppressive drugs (< 1 mg/day) for at least 3 days prior to and while receiving ALT-803
Chronic or long-term corticosteroids: ?0.5 mg/kg/day of oral prednisolone or equivalent
Sporadic corticosteroids: ?1 mg/kg/day of oral prednisolone or equivalent for 2 or more short courses of > 3 days
Prednisone dose ? 20 mg/day
Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization
Chronic systemic steroid therapy defined as prednisone or equivalent 10 mg/day or greater;
REGISTRATION TO TREATMENT (STEP 1): The patient has to be on first-line TKI therapy (the same TKI) for at least 2 years prior to registration\r\n* Dasatinib: 50 – 180 mg per day\r\n* Imatinib: 200 – 800 mg per day\r\n* Nilotinib: 300 – 400 mg every 12-24 hours
Steroid therapy, or steroid therapy with more than 7 consecutive days of steroids within the prior 4 weeks \r\n* The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is permitted\r\n* Inhaled or topical corticosteroids are permitted
Active immunosuppressive therapy, including concurrent systemic immunosuppressive therapy or steroid therapy with more than 7 consecutive days of steroids within the prior 4 weeks\r\n* The use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 10 mg/day) as replacement therapy is permitted\r\n* Inhaled corticosteroids are permitted
Patients must have clinical evidence* of steroid-refractory acute graft vs host disease (any organ) defined as one of the following:\r\n* Progressive GVHD after at least 3 days on corticosteroids (>= 1 mg/kg of prednisone or equivalent); this means new organ involvement (skin, liver, or intestine) or increased organ specific symptoms sufficient to increase the organ stage by one or more\r\n* No improvement in GVHD after at least 7 days on corticosteroids (>= 1 mg/kg of prednisone or equivalent)\r\n* Patients with protracted acute GvHD who are unable to be tapered below 0.5mg/kg/d of prednisone (without the addition of alternate immunosuppressives) are considered eligible
Patients receiving a stable dose (> 4 weeks) of corticosteroid therapy equivalent to 20 mg of prednisone per day or less are eligible
Patients must have completed prednisone taper (5 mg - 2.5 mg) prior to randomization
Subjects with progressive GVHD (ie, increase in stage in any organ system or any new organ involvement) after 3 days of primary treatment with methylprednisolone ? 2 mg/kg per day (or equivalent).
Subjects with GVHD that has not improved (ie, decrease in stage in at least 1 involved organ system) after 7 days of primary treatment with methylprednisolone ? 2 mg/kg per day (or equivalent).
Subjects who previously began corticosteroid therapy at a lower dose (at least 1 mg/kg per day methylprednisolone) but develop new GVHD in another organ system.
Any corticosteroid therapy for indications other than GVHD at doses of methylprednisolone or equivalent > 1 mg/kg per day within 7 days of enrollment.
Systemic steroid therapy or steroid therapy that cannot be discontinued with more than 7 consecutive days of steroids within the prior 2 weeks\r\n* Note: the use of prednisone or equivalent < 0.125 mg/kg/day (absolute maximum of 15 mg/day) as replacement therapy is permitted; inhaled or topical corticosteroids are permitted
Subject received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per day of prednisone within 4 weeks prior to day 1, intended for the treatment of prostate cancer.
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to study day
Previously untreated and not receiving any other agent that would be considered as a treatment for the lymphoma; for subjects with severe systemic symptoms, compressive disease, or rapidly progressing symptomatic adenopathy, are allowed for lymphoma associated symptom treatment with up to 1 mg/kg/day prednisone, or equivalent, for a maximum of 7 days is permitted prior to beginning the treatment, at the discretion of the investigator; a washout period does not apply
Chronic use of systemic corticosteroid above an accepted physiologic dose (5mg per day of prednisone or equivalent) within 7 days of enrollment except when used as premedication
Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks (28 days) prior to Day 1.
No prior anti-lymphoma therapy. However, for subjects with bulky disease,systemic symptoms, compressive disease, or rapidly progressing adenopathies, pre-phase treatment with 1 mg/kg/day prednisone, or equivalent, for a maximum of 7 days is permitted prior to Cycle 1 Day -6 at the discretion of the Investigator. In exceptional cases, if clinically indicated, a higher dose of steroids and/or a slightly longer duration is allowed for the purpose of urgent symptom management, and the subjects is considered eligible. A washout period does not apply. However the fresh core biopsy mentioned above should be performed before starting prednisone.
DONOR: Any contraindication to the administration of subcutaneous G-CSF at a dose of 16 mg/kg/day for 5 consecutive days
Any corticosteroid therapy (for indications other than GVHD) at doses > 1 mg/kg per day methylprednisolone or equivalent within 7 days of randomization.
No corticosteroid use will be permitted within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent
The patient must not be on a corticosteroid dose greater than physiologic replacement dosing defined as 30 mg of cortisone per day or its equivalent
Participants with ongoing corticosteroid use >30 mg per day of prednisone or equivalent
Use of prednisone (or equivalent corticosteroid dose) for SM up to 10 mg/day or its equivalent is allowed, but it cannot have been started during screening; patients who are on prednisone up to 10 mg/day for medical problems unrelated to SM are also permitted on study
Concurrent steroid use of more than an equivalent of 20 mg/day prednisone (or equivalent)
Current or recent (=< 10 days prior to randomization) use of aspirin (> 325 mg/day), or clopidogrel (> 75 mg/day)
Patients who are on high dose steroid (i.e. prednisone or equivalent more than 10 mg a day) or immune suppression medications
Patient has a medical condition that requires chronic systemic steroid therapy or requires any other form of immunosuppressive medication; however, patients using physiologic replacement doses of hydrocortisone, or its equivalent, will be considered eligible for this study; up to 20 mg hydrocortisone (or 5 mg of prednisone) in the morning and 10 mg hydrocortisone (or 2.5 mg of prednisone) in the evening
Participants must have steroid-refractory cGVHD; steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms; patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible
Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
Participants must have steroid-refractory chronic GVHD (cGVHD); steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms; participants with either extensive or limited chronic GVHD requiring systemic therapy are eligible
Participants with ongoing prednisone (equivalent) dose requirement > 1 mg/kg/day (or equivalent)
Corticosteroid therapies of > 20 mg/day prednisone, > 4 mg/day dexamethasone, > 80 mg/day hydrocortisone, or equivalent; oral, inhaled, or topical steroids are allowed during study as long as it does not exceed 80 mg/day hydrocortisone
Patients with medical conditions that require chronic systemic corticosteroid therapy or require any other form of immunosuppressive medication. However, patients using physiologic replacement doses of hydrocortisone, or its equivalent, will be considered eligible for this study: up to 20 mg hydrocortisone (or 5 mg of prednisone) in the morning and 10 mg hydrocortisone (or 2.5 mg prednisone) in the evening.
Steroid refractory cGVHD, defined as having persistent signs and symptoms of cGVHD despite ? 4 weeks of prednisone (or equivalent) dosed at ? 0.25 mg/kg/day (or ? 0.5 mg/kg every other day) within the 12 months prior to screening.
Stable dose of ? 1 mg/kg/day of systemic prednisone or equivalent for at least 2 weeks prior to first dose of AMG 592.
Has cGvHD that did not respond to high-dose corticosteroids (average 0.5 mg/kg/d prednisone for >= 8 weeks) or second-line systemic therapy
Patients can be enrolled and begin study therapy with ofatumumab within 14 days from initiation of 1 mg/kg/day prednisone for therapy of chronic GVHD
Patients with chronic graft versus host disease (GVHD) that involves 3 or more organs or with a score of 2 or greater in any single organ based on National Institutes of Health (NIH) cGVHD grading and have the following relationship with steroid:\r\n* Dependent disease - cGVHD manifestations requiring a glucocorticoid dose >= prednisone 0.25 mg/kg/day (0.5 mg/kg by mouth every other day) for at least 12 weeks\r\n* Refractory disease - Progressive cGVHD manifestations despite treatment with a glucocorticoid dose >= prednisone 0.5 mg/kg/day (1 mg/kg by mouth every other day) for at least 4 weeks\r\n* Steroid intolerant
Current or recent (=< 10 days prior to randomization) use of aspirin (> 325 mg/day), clopidogrel (> 75 mg/day), or prasugrel (> 10 mg/day)
The patient requires treatment with corticosteroids at a dose > 0.1 mg/kg/day or has a known allergy to DSMO
Clinically stable and off or on low dose (no more than 0.1 mg/kg/day, maximum of 4 mg/day dexamethasone) corticosteroid for at least 1 week prior to study enrollment
Corticosteroid doses > 10 mg/day of prednisone or equivalent within 14 days prior to cycle 1 day 1
Steroid dose not greater than 2 mg/kg prednisone equivalent at time of study enrollment; if patient has steroid refractory GVHD (defined as worsening of GVHD after 3 days of 2 mg/kg prednisone equivalent or no improvement after 7 days of 2 mg/kg prednisone equivalent), time interval from start of steroids to initiation of ECP should not be > 14 days
Platelet count > 600 × 10^9/L after 3 months of at least 2 g/day of hydroxyurea (2.5 g/day in subjects with a body weight over 80 kg) OR at the subject's maximally tolerated dose if that dose is < 2 g/day.
Patients requiring concurrent systemic steroid therapy higher than physiologic dosage (>10mg/day of prednisone or equivalent).
Inability to begin prednisone therapy at a dose of greater than 0.5 mg/kg/day.
Already receiving sirolimus (for prophylaxis or treatment of acute GVHD) with prednisone at ? 0.25 mg/kg/day (or equivalent) ± additional agents.
Ongoing corticosteroid use >30 milligrams per day (mg/day) prednisone or equivalent
Patients must have received a trial of corticosteroids equivalent to prednisone greater than or equal to 0.5 mg/kg/d for at least one month; OR at least one pulse of methylprednisolone at a dose at least 1000 mg/d for 3 days on at least one occasion within the previous 6 months prior to the transplant decision
Corticosteroid administration >20 mg/day of prednisone or equivalent within 14 days
Inclusion Criteria:\n\n        Male or female subjects may be entered in the study only if they meet all of the following\n        criteria:\n\n          1. Age ?18 and ?65 years of age.\n\n          2. Recipient of an allogeneic hematopoietic stem cell transplantation.\n\n          3. Steroid-resistant acute GvHD, Grade II-IV, defined as: progressive disease after 3\n             days of primary treatment with methylprednisolone 2 mg/kg, or equivalent; or lack of\n             at least a partial response after 7 days of primary treatment with methylprednisolone\n             2 mg/kg or equivalent; or lack of a complete response after 14 days of primary\n             treatment with methylprednisolone 2 mg/kg or equivalent. Note: Subjects who may have\n             received an increase in their steroid dose treatment prior to randomization will be\n             eligible for enrolment.\n\n          4. Evidence of myeloid engraftment (absolute neutrophil count ?0.5 x 10E9/L).\n\n          5. Karnofsky Performance Status score ?50%.\n\n          6. Adequate renal function as defined by serum creatinine ?2 × ULN or calculated CrCl of\n             ?30 mL/min using the Cockroft-Gault equation: Calculated CrCl= ([140-age in years] x\n             [ideal body mass {IB
Has primary steroid-refractory GvHD. Steroid-refractory disease is defined as worsening or no improvement in 5 to 7 days of treatment with methylprednisolone 2 milligram per kilogram (mg/kg) or equivalent or lack of a CR after 14 days of primary treatment with methylprednisolone 2 mg/kg or equivalent. Note that participants who develop intestinal GvHD while receiving systemic therapy for other GvHD are still eligible after 5 to 7 days, even if the intestinal GvHD has not been present for the entire duration. Participants who may have received an increase in their steroid dose treatment (example, increased methylprednisolone from 1 mg/kg to 2 mg/kg) before enrollment will be eligible, provided the participant has met the definition of steroid refractory above. Participants who develop toxicity on corticosteroids or who are otherwise medically unable to be dosed to this level, will also be eligible.
Patients with steroid refractory graft versus host disease (SRGvHD). SRGvHD is defined as progression (=increase in overall grade) after 5 days on ?2mg/kg methylprednisolone or equivalent OR no improvement (no decrease in overall grade) after 10 days on ? 2mg/kg methylprednisolone or equivalent. If patients are receiving steroids for GvHD prophylaxis as per center standard, progression after 5 days and no response after 10 days after doubling the steroid dose will be regarded as steroid refractory.
Patients must have failed at least two forms of immunosuppression:\r\n* Moderate-to-high dose corticosteroids (0.5-1 mg/kg/day**, and/or IV pulse methylprednisolone)\r\n** When cyclophosphamide is the accepted standard of care (renal and neurologic), the maximally tolerated dose of prednisone will be sufficient to meet the corticosteroid criterion\r\n* Azathioprine, methotrexate, cyclosporine, tacrolimus, belimumab, rituximab, or mycophenolate mofetil, in the case of severe and ongoing hemolytic anemia and/or thrombocytopenia, failure of intravenous immunoglobulin treatment will count as the second treatment
Receiving a new course of systemic corticosteroids (? 0.5 mg/kg/day) as first-line cGVHD therapy at least 1 day and no more than 21 days prior to first dose of ENTO/Placebo AND
Inability to begin systemic corticosteroids therapy at a dose of ? 0.5 mg/kg/day (or equivalent)
Patient has failed to respond to steroid treatment, with failure to respond defined as any Grade B-D (IBMTR grading) acute GVHD that shows progression within 3 days, or no improvement within 7 consecutive days, of treatment with 2 mg/kg/day methylprednisolone or equivalent.
Ongoing corticosteroid use >30 milligrams per day (mg/day) of prednisone or equivalent. Participants receiving corticosteroid treatment with less than equal to (</=) 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks duration prior to randomization (Cycle 1 Day 1)
On immunosuppressive or other anti-leukemic therapy, excluding patients receiving glucocorticoids for management of circulating blast count or patients on a stable dose (<20mg/m2/day prednisone or equivalent) of systemic or topical glucocorticoid therapy with ? Grade 1 GvHD or tapering dose of calcineurin inhibitor
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent within 14 days of first dose)
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization
Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within the last three weeks
Contraindication to any of the required concomitant drugs, including antiviral (e.g. Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in a dose equivalent to dexamethasone ? 1.5 mg/day or prednisone ? 10 mg/day. (Steroid use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.)
Ongoing corticosteroid use >30 mg per day prednisone or equivalent, for purposes other than lymphoma symptom control
Doses ? 10 mg/day prednisolone or equivalent is allowed, provided that the steroid dose has been stable or tapering for at least 14 days prior to the first dose of CA-4948
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.
Glucocorticoid use, unless given in doses less than or equal to 25mg/Day prednisone (or equivalent) for less than 7 Days for exacerbations other than CLL (e.g. asthma).*
Supraphysiologic doses of glucocorticoids (defined as > 30 mg of hydrocortisone per day or > 7.5 mg of Prednisone per day, or equivalent doses of other agents) or exposure to other immunosuppressive medications in the previous 30 days.
Chronic GVHD that did not respond to high-dose corticosteroids (prednisone at 1.0 mg/kg/day for at least 1 week or prednisone at 0.5 mg/kg/day or 1 mg/kg every other day for at least 4 weeks), or second-line therapy (any)
Steroid-Refractory/Dependent aGVHD (ARM 2)\r\n* Pediatric or adult HCT recipient with grade II-IV steroid refractory or steroid-dependent acute GVHD, defined as any one of the following:\r\n** No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent\r\n** Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent\r\n** Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent\r\n** Flare of acute GVHD of at least grade II/IV severity while on steroids at a dose > 0.1/mg/kg/day; this can include late-onset aGVHD and overlap syndrome
Patients receiving high dose opioids on a chronic basis (greater than or equivalent to 60 mg of morphine per day)
Patients requiring high doses of glucocorticosteroids (>= 0.3 mg/kg prednisone or its equivalent)
Receiving anastrozole (1 mg) or letrozole (2.5 mg) orally once a day, for >= 21 days prior to registration and plan to continue throughout the duration of study
Steroid dependent/refractory cGVHD defined as:\r\n* Steroid dependent disease: Persistent cGVHD manifestations requiring a glucocorticoid dose >= prednisone 0.25 mg/kg/day (0.5 mg/kg orally [po] every other day) for at least 12 weeks\r\n* Steroid refractory disease: Progressive cGVHD manifestations despite treatment with a glucocorticoid dose >= prednisone 0.5 mg/kg/day (1 mg/kg po every other day) for at least 4 weeks
Cancer patients with severe pain (i.e., >= 7 on NRS) already on opioid therapy for one week or longer, at least 60 mg of oral morphine/day, 25 mcg of transdermal fentanyl/hour, 30 mg of oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an equianalgesic dose of another opioid
Patients using >= 20 mg/day of prednisone (or steroid equivalent dose) for any chronic medical condition
Patients must have steroid refractory chronic (c) GVHD, defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 2 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms, or if not responding to any lines of therapy beyond steroids, or if the MD feels adding/increasing steroids would not be in the patient’s best interest
Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
Participants must have steroid-refractory chronic graft-versus-host disease (cGVHD); steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms; participants with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible
Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
Acute GVHD must be corticosteroid refractory as defined by:\r\n* Progressive GVHD after at least 3 days on corticosteroids (>= 1 mg/kg of prednisone or equivalent); this means new organ involvement (skin, liver, or intestine) or increased organ specific symptoms sufficient to increase the organ stage by one or more\r\n* No improvement in GVHD after at least 7 days on corticosteroids (>= 1 mg/kg of prednisone or equivalent) OR insufficient improvement which warrants the addition of another systemic agent at the opinion of the treating investigator\r\n* GVHD during taper of corticosteroids which is unable to be tapered below 0.5 mg/kg/day of prednisone equivalent or, in the opinion of the treating physician, requires addition of another systemic agent
Patients must have steroid refractory classic cutaneous, myofascial, or sclerodermatous cGVHD (+/- other organ involvement, clinically diagnosed), defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at >= 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms or if not improving on any line of therapy beyond steroids or if treating physician feels that increasing or adding steroids is not in the patient’s best interests; note that the dose of systemic steroids can certainly be lower than 0.25 mg/kg/day at enrollment
Ongoing prednisone requirement > 1 mg/kg/day (or equivalent)
Patients who have not shown a satisfactory response to methylprednisolone-equivalent doses at 2 mg/kg/day, based on adjusted body weight
Patients with steroid refractory chronic GVHD are defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at >= 0.5 mg/kg/day for at least 2 weeks in the preceding 24 months (or equivalent doses of alternate corticosteroids) without complete resolution of signs and symptoms
Requires immunosuppressive doses of corticosteroid therapy (> 10 mg/day prednisone equivalents) for >= 2 weeks prior to registration