relapsed and refractory multiple myeloma (RRMM): subjects who have received at least 2 prior regimen, were responsive to at least 1 prior regimen (as defined by IMWG criteria) and then are refractory to their most recent therapy (? 25% response or progression during therapy or within 60 days after completion of therapy). Prior therapies for subjects with PRMM or RRMM must include an immunomodulatory drug (IMiD) and a proteasome inhibitor as separate lines or a combined line of therapy. If prior therapy includes autologous stem cell transplantation (ASCT), then induction/ASCT/maintenance therapies will be considered as one line of therapy altogether. Subjects who have relapsed after ASCT or are unable to receive ASCT are eligible. The interval from ASCT to entry in the study must be ?12 weeks.
Have high-risk relapsed or refractory Hodgkin lymphoma (HL), defined as at least one of the following:\r\n* Primary refractory disease to front-line therapy\r\n* Relapse within 1 year of completing front-line therapy\r\n* Extranodal involvement at the time of pre-ASCT relapse\r\n* B symptoms at pre-ASCT relapse\r\n* More than one type of pre-ASCT salvage therapy required
Planning to receive or have received autologous stem cell transplantation (ACST) per institutional standards as part of standard of care\r\n* Pre-ASCT participants may consent but will not be eligible to begin treatment until after ASCT, and will have to fulfill all inclusion and exclusion criteria before starting protocol\r\n* All participants must initiate day 1 of protocol therapy within 30-60 days post stem cell reinfusion; study PI can grant exception for a patient to start as late as 75 days post stem cell reinfusion with a reasonable justification for a delay (e.g. recovery from post -ASCT toxicity) and this will not be a protocol deviation, nor require an exception to be filled
Recovery from ASCT toxicity as defined as outpatient status, able to drink, eat normally, and do not need intravenous hydration prior to day 1 of therapy
Post-ASCT anti-lymphoma or investigational therapy; immediate post-ASCT consolidative radiation therapy is allowed as long as it occurs prior to initiation of study therapy; baseline imaging and pulmonary function tests (PFTs) must be performed after completion of radiation
For lymphoma patients only: Participants must have received and relapsed after autologous stem cell transplantation (ASCT), or be ineligible for ASCT (including on the basis of refractory disease), or have declined ASCT
Completion of ASCT within 100 days prior to Day 1 of Cycle1.
Participants must have a pathologic diagnosis of classical Hodgkin lymphoma (cHL) who are relapsed or refractory with one of the following: I. Autologous stem cell transplant (ASCT) ineligible patients ii. Patients after failure of ASCT
Patients with relapsed or refractory classical HL who have previously received autologous stem cell transplant (ASCT); patients must have received prior ASCT at least 12 weeks (3 months) before the first dose of ibrutinib or patients with relapsed or refractory HL who have failed at least 2 lines of prior therapy and are not eligible for ASCT due to:\r\n* Inability to achieve a complete response (CR) or partial response (PR) prior to transplant\r\n* Age or comorbid conditions\r\n* Inability to collect stem cells
Patients must have received all approved therapies known to provide clinical benefit for their disease subtype and for which they are eligible or must have refused these treatment options prior to consideration for enrolment. In the case of patients who have lymphomas for which high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is considered a standard curative therapy, eligibility for this study requires that the patient's disease has relapsed after HD-ASCT, that the patient is not eligible for HD-ASCT, or that the patient has refused HD-ASCT.
Lenalidomide-related toxicities before ASCT necessitating its discontinuation as part of treatment
Have relapsed or treatment refractory disease with >= 10% CD138+ malignant plasma cells (IHC) on bone marrow (BM) core biopsy, either:\r\n* Following autologous stem cell transplant (ASCT)\r\n* Or, if a patient has not yet undergone ASCT, the individual must:\r\n** Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician, and,\r\n** Demonstrate disease that persists after > 4 cycles of induction therapy and that is double refractory (persistence/progression) after therapy with both a proteasome inhibitor and immunomodulatory drug (IMiD) administered either in tandem, or in sequence.
Previously treated ASCT naive MM patients, currently with relapsed or refractory disease who are being considered for single ASCT for relapsed disease; patients must be eligible to undergo a stem cell transplant as per institutional criteria for selection at the time of registration
Patients must be eligible to undergo high dose chemotherapy (HDT) followed by ASCT as a form of remission consolidation
Patients without evidence of documented disease progression clinically or radiographically after ASCT (stable disease [SD], partial remission [PR] or complete remission [CR]) who have had count recovery (absolute neutrophil count [ANC] > 500 cells/mm^3, non-transfused platelet count > 20,000 K/mm^3) and are at least 30 days post ASCT but no more than 120 days post ASCT
After failure of allogeneic stem cell transplant (ASCT) or after failure of frontline therapy in subjects who declined or are not ASCT candidates
PRE-ASCT ELIGIBILITY CRITERIA
Sufficient recovery from first or second ASCT within 60-120 days of transplant (Cohort C)
Have a contraindication to post-ASCT maintenance lenalidomide
For Part 2 and Part 3 of the study, participants that are eligible to undergo first time HD-ASCT.
Patients whose primary therapy was changed due to suboptimal response or toxicity will be eligible, however no more than 2 regimens will be allowed prior to ASCT
Prior high-dose chemotherapy (HDC)-ASCT
Patients must be between 100 to 180 days after ASCT
Dasatinib use prior to ASCT is allowed
Patients who have evidence of disease progression before day 100 after ASCT
Subjects must not be candidates for intensive high-dose chemotherapy, with or without an autologous stem cell transplant (ASCT), due to one or more of the following factors:\r\n* Age >= 65 years: Patients < 65 years of age must be ineligible for high-dose chemotherapy (HDT)/ASCT on the basis of comorbidity, organ dysfunction or patients refusal for HDT/ASCT\r\n* Comorbid disease, such as coronary artery disease (CAD), congestive heart failure (CHF), pulmonary dysfunction, liver or kidney dysfunction, precluding high dose therapy secondary to expected increased morbidity and mortality: poor performance status (Karnofsky performance scale [KPS] 70% or less); ejection fraction < 45%; impaired pulmonary function test with diffusing capacity of lung for carbon monoxide (DLCO) < 50% expected\r\n* Patient refusal\r\n* Medical conditions which in the opinion of the treating physician and DMT preclude HDT/ASCT
Patients must have disease that is recurrent or refractory to standard therapy; patients must have failed front-line therapy and declined or are not candidates for autologous stem cell transplant (ASCT) or have failed prior ASCT
Patients with planned standard of care ASCT using melphalan 200 mg/m^2
Eligibility for ASCT is determined by the above inclusion criteria.
Has received high-dose melphalan and autologous stem cell transplant (HDM-ASCT) within 12 weeks before the first infusion or are planning for HDM-ASCT
Refractory or relapsed HL patients that are also candidates for ASCT
30-120 days post ASCT for non-Hodgkin’s lymphoma
Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT
Participants who plan to proceed with ASCT as part of first line therapy
Histologically confirmed DLBCL at last relapse(by central pathology review before enrolment. .- Relapsed or refractory disease after ?2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT
Eligible for and consenting to ASCT
Relapsed following, or refractory to, previous ASCT
Refused intensification treatment and/or ASCT
Patients not considered in the opinion of the investigator eligible, or patients unwilling to undergo intensive salvage therapy including ASCT
Plasmacytomas > 1 cm in marrow areas measured by magnetic resonance imaging (MRI) or extramedullary plasmacytomas (radiated lesions are exempt from this criteria); patients may receive cytoreductive therapy, including allogeneic stem cell transplant (ASCT) (if high risk) or second ASCT (if failed a prior ASCT) to achieve disease control, but may not receive any cytoreductive therapy within 30 days of the dosimetry infusion and must have bone marrow cellularity meeting inclusion criteria obtained at least 21 days after any cytoreductive/myelosuppressive chemotherapy was last administered
Participants must be planning to receive or have received autologous stem cell transplantation; participants may enroll prior to ASCT, but will not be eligible to begin treatment until after ASCT, and must fulfill all inclusion and exclusion criteria at that time; ASCT will be performed according to institutional standards and is not a part of this study
No more than 1 line of anthracycline-containing chemotherapy prior to ASCT, and no more than 3 lines of therapy total prior to ASCT for arms A and B; no more than 1 line of therapy prior to ASCT for arm C
Participants must begin study treatment no later than 21 days from the post-ASCT discharge; additionally, they must have recovered from ASCT toxicities at the time of first study treatment; recovery from ASCT toxicity is defined using the eligibility criteria in this section, as well as outpatient status, ability to drink and eat normally, without the need for intravenous hydration; participants must be no later than 60 days from stem cell reinfusion; exceptions to these time frames may be made in discussion with the overall principal investigator (PI) and will not constitute study violations
Must have not received post-ASCT consolidation therapy.
Double (tandem) ASCT.
Relapsed or refractory after an autologous stem cell transplant (ASCT) or at least two prior multi-agent chemotherapy regimens in patients not candidates for ASCT
Must not be a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT
Suitable and interested to proceed to ASCT
Patients whose primary therapy was changed due to suboptimal response of toxicity will be eligible, however no more than 2 regimens will be allowed prior to ASCT
Dasatinib use prior to ASCT is allowed
Patients who have evidence of disease progression before day 100 after ASCT
Prior peripheral ASCT within 12 weeks of C1D1
If not previously transplanted, patient should be either ineligible for autologous stem cell transplant (ASCT), or must have declined the option of ASCT; patients who have previously had ASCT and have subsequently progressed are eligible, provided other entry criteria are met
Patient must have undergone ASCT between 60 and 90 days prior to study registration
Patient who shows evidence of progressive disease during salvage chemotherapy or following ASCT
Patients with HL who have received ASCT in the previous 30-45 days
Patients at high risk of residual HL post ASCT
Patients who were determined to have a best clinical response of progressive disease with salvage treatment immediately prior to ASCT
Post ASCT or current therapy with other systemic anti-neoplastic or investigational agents
Subject is eligible for and plans to undergo ASCT
ASCT within 4 weeks (i.e., ASCT is allowed if it occurred before enrollment in Study NEOD001-201 or after completion of Study NEOD001-201 if it was at least 4 weeks before Month 1-Day 1 of this study)
Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.
Refractory post-ASCT i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed subjects) ii. If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy
Eligible for ASCT
Patient either is not a candidate for autologous stem cell transplant (ASCT), has declined the option of ASCT, or has relapsed after prior ASCT.
Prior to enrollment on ANBL0032, a determination of mandatory disease staging must be performed (tumor imaging studies including computed tomography [CT] or magnetic resonance imaging [MRI], MIBG scan, and vanillylmandelic acid [VMA]/homovanillic acid [HVA]; bone marrow aspirates are required but biopsy may be omitted if negative prior to ASCT); this disease assessment is required for eligibility and should be done preferably within 2 weeks, but must be done within a maximum of 4 weeks before enrollment\r\n* For those with residual disease before radiotherapy, re-evaluation of irradiated residual tumors is preferably performed at the earliest 5 days after completing radiotherapy; patients with residual disease are eligible; biopsy is not required; patients who have biopsy proven residual disease after ASCT will be enrolled on Stratum 07\r\n* Patients must not have progressive disease at the time of study enrollment except for protocol specified bone marrow response and except for elevations of catecholamines as the only sign of disease in a patient who had normal catecholamines at pre-ASCT evaluation
Patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than ten (10) calendar days after the date of study enrollment; patients should be enrolled preferably between day 56 and day 85 after peripheral blood stem cell (PBSC) infusion (day from 2nd stem cell infusion for tandem transplant); patients must be enrolled no later than day 200 after PBSC infusion; enrollment must occur after completion of radiotherapy, and after completion of tumor assessment post-ASCT and radiotherapy; informed consent should be obtained within 3 weeks pre-ASCT up to the time of registration
For post autologous stem cell transplant (ASCT) patients, salvage therapy plus ASCT just prior to MDV9300 treatment must have resulted in a PR or stable disease;
Scheduled to have high-dose chemotherapy and ASCT
Treatment plan for HDC-ASCT