Participant must obtain prior approval from insurance to reimburse for oral temozolomide for the duration of the study or agree to self-pay for oral temozolomide
the safety or well-being of the participant or study staff
Participant must consent to provide the following for biomarker analyses:
Participant has prior exposure to any pyrrolobenzodiazopine-containing agent
Participant has a history of major immunologic reaction to any Immunoglobulin G (IgG).
Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications is to be documented in the medical record corresponding with the consent conference.
The participant has any known significant ophthalmologic abnormalities of the surface of the eye.
Progressive disease during the antecedent protocol. If approval to treat beyond progression was already given in the antecedent protocol, the participant may roll over into the current protocol without sponsor approval. Under special circumstances, enrollment into this protocol and dosing beyond progression may be considered and will require approval of the sponsor Participants meeting any of the following exclusion criterion of the antecedent study at the time the participant is considered for the extension (rollover) study:
Participant provides informed consent for prospective collection of relevant medical records for analysis of clinical outcome and treatment-planning techniques
Significant allergy to a biological pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the participant.
Participant must have progressed on the most recent therapy.
Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate participant participation in the clinical study (e.g., chronic pancreatitis, active hepatitis, etc.).
Participant is ? 30 days and ? 90 days from hematopoietic cell infusion.
Participant has achieved engraftment. Engraftment is defined as ANC ? 500 cells/?L and platelets ? 20000/?L on 3 consecutive measurements (each occurring at least 1 day apart). The participant must not have had a platelet transfusion within 7 days prior to the first measurement.
Participant meets the following criteria as indicated on the clinical laboratory tests:
Participant requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the participant.
Participant has active hepatitis C infection as determined by NAAT. NAAT must be performed if the participant has positive serology for hepatitis C. Participants who have had past exposure and have no detectable virus either through spontaneous clearance or treatment are eligible.
Participant requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR or sigma nonspecific receptor with the exception of drugs that are considered by the investigator to be absolutely essential for the care of the participant and for which no acceptable alternative exists.
Participant has a lesion in the oral cavity or oropharynx that is not yet biopsied but is highly suspicious for cancer; (randomization will be placed on hold until the presence of cancer is histologically confirmed, and a treatment plan is established; if the presence of cancer is not confirmed, the participant will be considered a screen failure)
Participant is scheduled for an end of study biopsy within 22 days of starting study agent and within 36 days of their study screening visit; (if the participant is scheduled for surgical excision of the tumor and the surgery is delayed for any reason after the participant has started taking the study agent, study agent dosing may be extended up to a maximum of 25 days without compromising the evaluability of the end of study biomarkers)
Participant has a history of hypoglycemia
Participant has a history of macular edema
Participant in other clinical trials
RETREATMENT WITH MODIFIED T-CELLS INCLUSION CRITERIA: Research participant without clinically significant encephalopathy/new focal neurologic deficits
RETREATMENT WITH MODIFIED T-CELLS EXCLUSION CRITERIA: Research participant with current evidence of GVHD
EXCLUSION - PARTICIPANT: Participant received prior chemotherapy or any other targeted therapies within the past 28, or palliative radiation within the past 14 days, prior to going on-study.
STRATUM A: Participant must be able to swallow medication; it is acceptable to administer medication via a gastrostomy tube (g-tube) if participant has a g-tube; it is not acceptable to place a g-tube for the purpose of delivering study medication
STRATUM B: Participant must be able to swallow medication; it is acceptable to administer medication via a g-tube if participant has a g-tube; it is not acceptable to place a g-tube for the purpose of delivering study medication
STRATUM C: Participant must be able to swallow medication; it is acceptable to administer medication via a g-tube if participant has a g-tube; it is not acceptable to place a g-tube for the purpose of delivering study medication
Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
Research participant has a released cryopreserved CAR T cell product
Research participant serum total bilirubin or transaminases does not exceed 2 x normal limit
Research participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell dose
Participant has received treatment with the following:
Patient has a planned complete macroscopic cytoreduction (visual) (CC0) cytoreduction – NOTE: registration occurs during surgery and not before; if, during surgery, the principal investigator (PI)/sub-investigator (SubI) discerns that all disease cannot be removed surgically, the participant will be considered a “screen failure”, HIPEC will not be performed, and the participant will be removed from the study
The participant is unable to swallow oral dosage forms
The reason a participant is not eligible should be documented in the electronic case report form (eCRF).
Failure of research participant or legally responsible parent or guardian to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study.
Participant with a history of cirrhosis or other indication of significant possible hepatic dysfunction. Note: Those with non-alcoholic steatohepatitis (NASH) should be discussed with the AbbVie TA MD before enrollment.
Participant with a positive diagnosis of hepatitis A, B, or C.
Total bilirubin: =< 1.5 institutional upper limit of normal (ULN); if potential due to lymphoma, the first cycle may be given without ibrutinib and if transaminitis and bilirubinemia improves to meet parameters, participant mat be enrolled on the clinical trial
For Combination therapy, participant must not have had prior exposure to Rovalpituzumab Tesirine or a pyrrolobenzodiazepine (PBD) based drug.
Participant already enrolled in the study who has received at least one S64315 infusion.
The participant is on ixazomib monotherapy or on a drug combination with another medication, established while in his/her parent study; and
The participant meets any of the criteria for treatment discontinuation in the parent study.
Participant requires, or is likely to require, more than a two-week course of corticosteroids for intercurrent illness; participant must complete the course of corticosteroids 2 weeks before screening to meet eligibility
Participant is receiving medication(s) that might affect immune function
Investigator considers participant ineligible for intensive induction therapy based on medical reasons, disease characteristics such as genetics, type of AML (de novo or secondary), or participant characteristics such as age, performance status, co-morbidities, organ dysfunctions, or patient election of low-intensity treatment.
Participant has received no more than 1 other therapeutic regimen other than those listed above in (5).
Indications that participant is not appropriate for the study (e.g., aggressive, intoxicated, disruptive, visibly ill)
ELIGIBILITY CRITERIA FOR T-CELL PRODUCT INFUSION: Research participant without clinically significant encephalopathy/new focal neurologic deficits
ELIGIBILITY CRITERIA FOR T-CELL PRODUCT INFUSION: Research participant is not receiving systemically administered steroid therapy; glucocorticosteroid physiologic replacement therapy for management of adrenal insufficiency is allowed
RETREATMENT WITH MODIFIED T CELLS: Research participant without clinically significant encephalopathy/ new focal neurologic deficits
Be the only participant in his/her household
Research participant has a released cryopreserved T cell product
Research participant does not have a fever exceeding 38.5° Celsius (C); there is an absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to T cell infusion and/or there aren’t any indications of meningitis
Research participant serum total bilirubin does not exceed 2 x normal limit
Research participant transaminases does not exceed 2 x normal limit
Research participant does not have uncontrolled seizure activity following surgery prior to starting the first T cell dose
Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
Neurosurgeon finds the prospective participant is able to undergo neurosurgery
ELIGIBILITY TO UNDERGO LYMPHODEPLETION\r\nNote: evaluation should be performed no more than 7 days prior to lymphodepletion\r\n* Research participant with central nervous system (CNS) leukemic involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation but effectively treated to completion remission (< 5 white blood cell[WBC]/mm^3 and no blast in cerebrospinal fluid [CSF]) is eligible to proceed with lymphodepletion\r\n* Research participants must have a donor or stem cells source identified for allogeneic transplantation, either related (7/8 or 8/8 allele matched or haploidentical), unrelated 7/8 or 8/8 allele match) donor, or cord blood stem cell source (at lease 4/6 matched)\r\n* Research participants with a response less than a CR or complete response with incomplete hematopoietic recovery (CRi) or detectable minimal residual disease (MRD) positive disease\r\n* Research participant has a released cryopreserved T cell product for CAR T cell infusion on approximately day 0\r\n* Research participant must be at least 2 weeks out from having received the last dose of investigational agent\r\n* Karnofsky performance status (KPS) >= 70\r\n* Documented measurable or evaluable disease\r\n* Non hematological toxicity related to prior therapy must either have returned to =< grade 2, baseline, or deemed irreversible\r\n* Research participants of reproductive potential must agree to use and utilize and adequate method of contraception throughout treatment and for at least 8 weeks after T cell infusion\r\n*If a research participant has undergone prior allogeneic stem cell transplant, he/she must be off all immunosuppressants for GVHD for at least 7 days before beginning lymphodepletion\r\n* Pulmonary: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air\r\n* Cardiovascular: not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension\r\n* Renal Function: calculated creatinine clearance (absolute value) of >= 50 mL/minute or creatinine < 2.0 mg/dl or < 2 times upper limit of normal for the research participant's age group\r\n* Liver Function: adequate liver function defined as total bilirubin =< 3.0 mg/dl \r\n* ALT and AST =< 5 times the institutional upper limits of normal\r\n* Neurological: research participant without clinically significant encephalopathy/new focal deficits\r\n* Infectious diseases: no clinical evidence of uncontrolled active infectious process
ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED T CELLS\r\n* Research participants has undergone lymphodepletion\r\n* Pulmonary: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air\r\n* Cardiovascular: not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension\r\n* Renal Function: calculated creatinine clearance (absolute value) of >= 50 mL/minute or creatinine < 2.0 mg/dl or < 2 times upper limit of normal for the research participant's age group\r\n* Liver Function: adequate liver function defined as total bilirubin =< 3.0 mg/dl\r\n* ALT and AST =< 5 times the institutional upper limits of normal\r\n* Neurological: research participant without clinically significant encephalopathy/new focal deficits\r\n* Infectious diseases: no clinical evidence of uncontrolled active infectious process\r\n* Research participant must be off all anti-leukemic drugs, with the exception of the lymphodepleting regimens, at least 7 days prior to CAR T cell infusion
Study-Specific Exclusion\r\n* Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study\r\n* History of allergic reactions attributed to compounds of similar chemical or biological composition to cetuximab\r\n* Dependence on corticosteroids:\r\n** If the participant is undergoing leukapheresis: physiological replacement doses of steroids are allowed - prednisone no more than 7.5 mg, hydrocortisone less than 12 mg.m^2/day\r\n*** However, all participants must be able to reduce steroid requirement to no more than physiological replacement doses prior to start of lymphodepletion\r\n* Active autoimmune disease requiring systemic immunosuppressive therapy
Research participant must be at least 2 weeks from having received the last dose of immunosuppressant medications (e.g. calcineurin inhibitors, methotrexate, immunosuppressive antibodies, etc)
Research participant has a released cryopreserved T cell product for T cell infusions on approximately day 0
Research participant without clinically significant encephalopathy/new focal deficits
(ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS): Research participant without clinically significant encephalopathy/new focal deficits
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study
If the research participant is to undergo leukapheresis, he/she must must have a serum bilirubin =< 2.0 mg/dl\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease, the participant will still be considered eligible
If research participant is undergoing leukapheresis and the research participant has undergone prior alloSCT, two months must have elapsed since allogeneic stem cell transplant to undergo PBMC collection for T cell manufacturing
Research participant has a released cryopreserved T cell product for T cell infusion on approximately day 0
Total bilirubin =< 2.0 mg/dL\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
ALT and AST =< 2.5 times the institutional upper limits of normal\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
Research participant has undergone lymphodepletion
Liver function: total bilirubin =< 2.0 mg/dL\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
Liver function: ALT and AST =< 2.5 times the institutional upper limits of normal\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
Research participant without clinically significant encephalopathy/new focal deficits
Research participant is scheduled for an alloSCT
Research participant has >= 1% chimeric antigen receptor (CAR) modified T cells in the peripheral blood
Liver function criteria: total bilirubin =< 2.0 mg/dL\r\n* Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
Neurological: research participant without clinically significant encephalopathy/new focal deficits
Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy\r\n* Note: Please note that the above criterion is not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study
Failure to confirm diagnosis of cancer in participant
Participant has received prior therapy with a BH3 mimetic.
Participant screening laboratory result must indicate HCV genotype 1, 4, 5 or 6-infection if historical result is not available.
Participant is not suitable for receiving ocular steroids with conditions as described in the protocol.
Participant has had laser-assisted in situ keratomileusis (LASIK) procedure within the last 1 year or cataract surgery within the last 3 months.
safety or well-being of the participant or offspring
Participant may be either previously untreated for KS or refractory to or intolerant of any one or more prior KS therapies
Patient re-enrollment: this study permits the re-enrollment of a participant who has discontinued the study due to pre-treatment failure (ie, participant has not been treated); if re-enrolled, the participant must be re-consented
Written informed consent obtained from study participant or study participant’s legal representative and ability for study participant to comply with the requirements of the study
Type of Participant and Target Disease Characteristics
The participant is receiving therapy with any of the following:
The participant has either of the following:
The participant does not have:
Eligibility based on prior treatment with immunomodulatory agents depends on the mechanistic class of the drug and the cohort for which the participant is being considered
Given that the physician may select from an offered list of regimens to treat a specific participant, the participant may be refractory to an agent/s listed within the list of offered treatment choices
safety or well-being of the participant or offspring
Has fulfilled the following additional requirements regarding prior treatments for recurrent ovarian cancer (ROC) depending on the cohort participant is to be enrolled. Each participant must have documented evidence of clinical response or disease stabilization to the last regimen received.
The participant has:
Participant is amenable to compliance with protocol schedules and testing
Participant has had an allogenetic tissue/solid organ ransplant.
The participant has not received any previous treatment with anthracyclines.
The participant has squamous cell or undifferentiated gastric cancer.
Participant has chronic respiratory disease that requires continuous oxygen use.
Family relative or close friend is a trial staff member or a study participant
If a participant has received subsequent anticancer therapy (salvage therapy), the participant must have a \wash-out period\ defined as 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the planned start date of daratumumab monotherapy. The only exception is the emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day for a maximum of 4 days) before Daratumumab monotherapy
Research participant has a released cryopreserved T cell product
Research participant without clinically significant encephalopathy/new focal deficits
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study; a legal guardian may substitute for the research participant
safety and well-being of the participant or offspring
The participant must have undergone definitive surgical treatment for the current malignancy.
The participant must be randomized within 16 months from the time of surgery.
Written consent by the participant
Participant with evidence of recurrent malignancy
Participant with severe sepsis involving at least 1 organ failure
Participant is a family member or employee of the investigator
The participant is able to carry out daily life activities without difficulty
The participant does not have significant side effects from previous anti-cancer treatment
The participant has received anticoagulant therapy with the exception of aspirin within 1 week of starting the study
Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s) (eg, blood tests and ECG), that in medical judgment of the investigator may impede the participant's participation in the study, pose increased risk to the participant, and/or confound the results of the study
Participant is a family member or employee of the investigator
Participant must have viable alternatives to the current ART regimen in the event of drug resistance related to study treatment
If participant is HIV positive, participants must be on a stable antiretroviral regimen for at least 12 weeks prior to study enrollment
The participant has radiologically documented evidence of major blood vessel invasion or encasement by cancer
Participant who received a prior treatment intended for antitumor effect (medication, surgery, radiotherapy, etc.) within 4 weeks prior to the planned first day of study drug dosing (or participant who received mitomycin C or Nitrosourea within 6 weeks prior to the planned first day of study drug dosing).
Participant with leukemia has M2 or M3 marrow at the time of enrollment; participant with M2 marrow must have definite cytogenetic, molecular, or immunophenotypic evidence of recurrent/refractory disease
Participant disease tested positive for FLT3-ITD or –TKD within 60-day screening period
For participants potentially receiving chemotherapy: if the participant has received prior bendamustine, response duration must have been greater than (>) 1 year
PART II: Per oncologist responsible for management of care or follow up, participant must have a predicted lifespan of 6-months or more
Any disorder or disease, or clinically significant abnormality on laboratory or other clinical test(s), that in medical judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study
Participant is a family member or employee of the investigator
In the opinion of the investigator the protocol treatment is appropriate for the participant
The participant has superior vena cava syndrome contraindicating hydration.
The participant has metastatic disease at the time of study entry
The participant's tumor has Ki-67 expression ? 20%
The participant is receiving depot octreotide therapy at the time of enrolling into the study
The participant has received therapeutic radiolabeled somatostatin analogues
The participant has a history of treatment with other agents targeting the IGF receptor
Able to participate in patient-report outcomes (MDASI-BT, DSQ-C, LASA) questionnaires; assistance by research personnel is acceptable if participant has disabilities that make reading or writing difficult
Participant must be scheduled for a total laparoscopic or robotic-assisted hysterectomy for a gynecologic condition
Participant is not eligible if the surgeon does not plan to use a uterine manipulator
Prior treatment with a regimen that includes the combination drug will not necessarily exclude a participant from that cohort if the investigator views treatment with that agent as appropriate. However, a participant who has a contraindication for a particular combination agent or who has been discontinued from prior therapy with a particular agent for toxicity will not be eligible for inclusion in that particular cohort.
The participant has access to short message service (SMS) text messaging or email
PROVIDER ELIGIBILITY: The participant is willing to provide informed consent in English
PROVIDER ELIGIBILITY: The participant is a healthcare provider at Columbia University Medical Center with a high-risk patient identified in the research database (IRB-AAAO1761 or IRB-AAAP4151)
Co-parents must reside with the consenting eligible cancer participant (and child) at least 50% of the time and be actively participating in the care of the child
WEBSITE VISITORS: Have visited the personal website of a PCO participant
WEBSITE VISITORS: Have not visited the personal website of a PCA participant
Participant had recent surgery (within two weeks)
Participant has any metallic object in or around their head
Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this pilot study; a legal guardian may substitute for the research participant
Sufficient proficiency and confidence to use the internet and follow video-based instructions, as determined by the eligibility questionnaire to be completed by the participant
Any participant who has urologic cancer or is enrolled in a competing trial
Participant must have non-curable cancer as judged by the primary oncologist
Participant must be cognitively intact as judged by their responsible clinician
Participant must not have already worked with the staff writer at Dartmouth Hitchcock prior to enrollment in this study
Participant must not have physical symptoms that they feel would interfere with creative writing
Participants with a diagnosis of diabetes, unless they are able to provide a letter from a physician who will continue to monitor the participant during the research study
Current St. Jude LIFE participant
Participant has ongoing hemolysis.
Participant has history of major immunologic reaction to any auristatin-based and /or Immunoglobulin G (IgG) containing agent.
Clinician believes that eradication of concomitant HSIL is reasonable and feasible based on the extent of disease and overall medical condition of the participant
Participant plans to relocate away from the study site during study participation
The participant received prior immunotherapy and is experiencing or has experienced any of the following (OLE cohort only):
The participant received prior immunotherapy and at the time of study enrollment, requires steroids or other immunosuppressive agents (OLE cohort only).
A St Jude Life participant who was previously treated at St. Jude Children's Research Hospital (SJCRH)
Participant is 10 or more years from diagnosis
Participant has a Full Scale Intelligence Quotient (FSIQ) score > 79
Female research participant of childbearing age and male research participant of child fathering potential must agree to use safe contraceptive methods
Participant is employed in a position that requires night work (i.e. 10 pm to 6 am)
Primary treating oncologist for at least one patient participant
Permission from participant's physician
Participant not planning on remaining at St Jude for at least 4 weeks
Participant is enrolled on Total XVI
Participant is receiving gabapentin for another indication at the time of diagnosis of NP/PN or has received gabapentin previously
Participant will not or cannot provide medical records of past/present clinical exams (including but not limited to palpation, mammograms, biopsies, and ultrasound) if needed
Participant will not sign “Waiver of Diagnosis” form
Participant has symptoms related to HSIL and would benefit more from immediate treatment than from entry into the study and potential for randomization to active monitoring arm
Participant must have a gynecology examination within the last 5 years (gynecology examination is not required if participant had a hysterectomy), with no atypical hyperplasia and no cancer
H/L: Participant whose medical records or self-report indicate an ethnicity aside from Hispanic.
Be the only participant in his/her household on active treatment in Protocol 2016-0626 at the time.
Be the only participant in their household
Be the only participant in their household
Participant must be receiving a planned lymphoscintigraphy procedure
Participant has
the safety or well-being of the participant or study staff
STUDY PARTICIPANT ELIGIBLITY:
Participant must be a hematologist, oncologist, nurse practitioner, or physician assistant who practices medicine in the Duke Cancer Network
The participant has a medical or psychological condition that would not permit the participant to complete the study or sign informed consent.
The participant has a medical or psychological condition that would not permit the participant to complete the study or sign informed consent.
Female participant must be scheduled for a total laparoscopic or robotic-assisted hysterectomy for a gynecologic condition
Female participant is not eligible if the surgeon does not plan to use a uterine manipulator