Clinical Trials Actively Recruiting

Objective:

Co-Primary Objectives:

• To compare the 3-year milestone progression free survival (PFS) probabilities in participants with previously untreated, low tumor burden follicular lymphoma randomized to the rituximab arm versus the mosunetuzumab arm.
• To compare progression free survival (PFS) in participants with previously untreated, low tumor burden follicular lymphoma randomized to the rituximab arm versus the mosunetuzumab arm.

Secondary Objectives:

• To compare overall survival (OS) between participants randomized to rituximab versus mosunetuzumab.
• To compare overall response rates at the Week 40 assessment between participants randomized to rituximab versus mosunetuzumab.
• To compare event free survival (EFS) between participants randomized to rituximab versus mosunetuzumab.
• To compare the frequency and severity of toxicities between participants randomized to rituximab versus mosunetuzumab.
• To compare the restricted chance of longer PFS (2-6 years) between participants randomized to rituximab versus mosunetuzumab.

Objective:

Part A

Primary Objective:

• To compare the MMR rate at 24 weeks for olverembatinib versus bosutinib

Secondary Objectives:

• To compare the MMR rate at 96 weeks for olverembatinib versus bosutinib
• To compare additional parameters of the efficacy of olverembatinib versus bosutinib
• To compare the safety profile of olverembatinib versus bosutinib
• To characterize the Population PK of olverembatinib in the CML-CP population
• To evaluate Patient-Reported Outcome (PRO) measures of olverembatinib
• To evaluate Health Economics Outcomes Research (HEOR) measures of olverembatinib

Part B

Primary Objective:

• To evaluate the MMR rate by 24 weeks of olverembatinib in CML-CP patients with T315I mutation

Secondary Objectives:

• To evaluate the MMR rate by 96 weeks of olverembatinib in CML-CP patients with T315I mutation
• To compare additional parameters of the efficacy of olverembatinib in CML-CP patients with T315I mutation
• To evaluate the safety profile of olverembatinib in CML-CP patients with T315I mutation
• To characterize the population PK of olverembatinib in the CML-CP population with T315I mutation
• To evaluate PRO measures of olverembatinib
• To evaluate HEOR measures of olverembatinib

Objective:

Primary Objective:

• Estimate GVHD-free failure-free survival (GFFS) (a composite end point of survival without Grade III-IV aGVHD, cGVHD requiring immunosuppression, or primary or secondary graft failure requiring second definitive therapy) at 1 year after initiation of conditioning. GFFS will be evaluated separately for each transplant cohort.

Secondary Objectives:

• Estimate OS at 1 year after initiation of conditioning.
• Estimate FFS (a composite end point of survival without initiation of treatment with a second definitive therapy for curative intent) at 1 year after initiation of conditioning.
• Estimate the probability of being engrafted (i.e., without primary or secondary graft failure) and alive at 1 year after initiation of conditioning.
• Estimate the cumulative incidences of neutrophil recovery at Day +28 and Day +56 post-HSCT, platelet recovery at Day +100 post-HSCT, and red blood cell recovery at Day +100, Day +180, and Day +365 post-HSCT.
• Estimate the cumulative incidences of primary, secondary, and any graft failure at 1 year post-HSCT.
• Estimate the hematologic response classification according to the NIH criteria at Day +100, Day +180, and Day +365 post-HSCT.
• Estimate the cumulative incidences of Grade II-IV and Grade III-IV aGVHD at Day +100 post-HSCT.
• Estimate the cumulative incidences of all cGVHD and cGVHD requiring immunosuppression at 1 year post-HSCT.

Objective:

Dual Primary Objectives:

• To compare progression-free survival (PFS) in frail or selected intermediate fit
  Newly Diagnosed Multiple Myeloma (NDMM) participants treated with VRd-Lite
  induction followed by Lenalidomide maintenance (Arm 1) versus DRd induction
  followed by Lenalidomide maintenance (Arm 2).
• To compare overall survival (OS) in frail or selected intermediate fit NDMM
  participants treated with VRd-Lite induction followed by lenalidomide maintenance
  (Arm 1) versus DRd induction followed by lenalidomide and daratumumab and
  hyaluronidase-fihj maintenance (Arm 3).

Secondary Objectives

• To compare PFS in Arm 1 versus Arm 3
• To compare OS in Arm 1 versus Arm 2.
• To compare OS in Arm 2 versus Arm 3, contingent upon significant results from both dual primary endpoints in favor of the respective experimental arms.
• To compare the overall response rate (ORR) of Arm 1 against the ORR of Arm 2 and Arm 3.
• To assess the safety of Arm 1 with the safety of Arm 2 and Arm 3.
• To explore veinous and arterial thrombo-embolism (VTE) incidence in participants receiving lenalidomide during induction across the three study arms.
• To describe median time to response (CR or better per IMWG criteria, VGPR or better per IMWG criteria, PR or better per IMWG criteria) on the three study arms.

Objective:

Primary Objective:

• To compare major organ deterioration progression-free survival between participants randomized to the ASCT and non-ASCT arms of this study.

Secondary Objectives

• To compare overall survival (OS) between participants randomized to the ASCT and non-ASCT arms of this study.
• To compare rates of cardiac and renal organ responses between participants randomized to the ASCT and non-ASCT arms of this study.
• To compare rates of cardiac and renal organ progression between participants randomized to the ASCT and non-ASCT arms of the study.
• To compare the frequency and severity of toxicities between participants randomized to the ASCT and non-ASCT arms of this study.
• To compare minimal residual disease (MRD) negativity rates between participants randomized to the ASCT and non-ACST arms of this study.

Objective:

Primary objective:

• To compare time to first progression or death (PFS1) with continuous treatment (Arm A) and time to second progression or death (PFS2) with intermittent treatment that is restarted at first progression (Arm B). PFS1 and PFS2 will be defined as follows for patients who achieve complete remission (CR) with induction therapy and are randomized to a maintenance treatment arm:
  • Continuous treatment Arm A: time from randomization until first progression or death from any cause (PFS1)
  • Intermittent treatment Arm B: time from randomization until second progression or death from any cause (PFS2)

Key secondary objective:

• To compare overall survival between patients who achieve a CR with induction therapy subsequently treated with continuous treatment vs. intermittent treatment as part of maintenance therapy.

Secondary objectives:

• To determine overall response rate (ORR) and CR rate to induction therapy with zanubrutinib and rituximab in previously untreated MCL
• To determine adverse events during induction and post-induction in each study arm (Arm A and B) by CTCAE 5.0
• To determine PFS1, event free survival (EFS) and overall survival (OS) in each study arm (A and B)
• To determine the overall response rate (ORR) and complete response rate (CR) after restarting zanubrutinib, following the first progression, in the intermittent treatment arm (Arm B)
• To compare burden of symptomatic AEs as assessed by PRO-CTCAE between patients randomized to Arm A versus Arm B.

Objective:

Primary Objectives:

• To compare measurable residual disease (MRD) negative complete remission (CR) rates between each of the experimental regimens and Cytarabine + Daunorubicin (7+3).

Secondary Objective:

• To estimate the frequency and severity of toxicities with each of the regimens.
• To estimate complete remission (CR) rates, complete remission with incomplete count recovery (CRi, with and without MRD) rates, event-free survival (EFS), time to relapse, relapse-free survival (RFS), and overall survival (OS) with each of the regimens.
• To describe and compare MRD negative CR rates by genomic subgroups within and across randomized arms.

Objective:

Primary Objectives:

• To compare the progression-free survival in participants with relapsed/refractory
  large B-cell lymphoma or follicular lymphoma grade 3B with stable disease (SD)
  or partial remission (PR) on first imaging response by central review (day +30
  PET/CT scan) after commercial CD19 CAR T-cell therapy who are randomized to
  receive each consolidation therapy versus those that receive no consolidation
  therapy (i.e. control). Specifically, to compare the PFS of 1) mosunetuzumab
  consolidation to no consolidation, 2) polatuzumab vedotin consolidation to no
  consolidation, 3) mosunetuzumab + polatuzumab vedotin to no consolidation

Secondary Objectives:

• To compare overall survival (OS) in participants randomized to each consolidation
  treatment arm versus control.
• To compare the complete remission (CR) conversion rate up to one year in
  participants randomized to each consolidation arm versus control.
• To evaluate the treatment-related adverse events in participants randomized to
  each consolidation arm.
• To evaluate the association between total metabolic tumor volume (TMTV), SUV
  max, and sum product (SPD) of diameters by PET-CT at first imaging response
  with complete remission conversion up to one year in participants randomized to
  each consolidation arm as well as those randomized to control.
• To evaluate the overall response rate (ORR), CR rate, PFS, and OS of participants
  randomized to Arm 4 (observation) who have lymphoma progression within 12
  months of CAR T-cell infusion and subsequently ‘cross-over' to receive treatment
  with mosunetuzumab + polatuzumab vedotin.
• To estimate overall survival for all patients registered to this study.
• To assess the difference in overall survival between participants who achieved CR
  at first imaging (day +30) versus. those who did not achieve CR at first imaging.

Objective:

Primary Objective:

• To demonstrate improvement in progression free survival (PFS) in the autologous stem cell transplant (ASCT) arm compared to the observation arm.

Secondary Objectives:

• To assess difference in overall survival (OS) between the observation and autologous stem cell transplant (ASCT) arm.
• To evaluate the differences in study intervention benefit for PFS and OS by the randomization stratification factors (histology and choice of induction chemotherapy).
• To evaluate the cumulative incidence of relapse and mortality between the observational and autologous stem cell transplant (ASCT) arm.

Objective:

Primary Objective:

The primary objective of the randomized, dose finding portion of the trial is to compare the safety, feasibility, and efficacy of two ruxolitinib doses in the setting of GVHD prophylaxis. In this portion of the study, these three evaluations will be assessed by:

• Safety: graft failure by Day 28 and overall mortality by Day 100
• Feasibility: proportion of participants requiring dose reduction or interruption by Day 100
• Efficacy: Grade II-IV acute GVHD-free survival by Day 100

The primary objective of the randomized Phase III portion of the trial is to compare GFS up to 24 months after HCT between Tac/MTX/Rux versus PTCy/Tac/MMF. There are co-primary objectives of demonstrating non-inferiority and superiority on the primary endpoint of GFS. An event for this time to event outcome is defined as Grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, or death by any cause.

Secondary Objectives:

Secondary objectives are the following comparisons between the two treatments in the Phase III portion based on:

• GVHD-free and relapse/progression-free survival
• Rates of NIH mild, moderate, and severe chronic GVHD (defined by the NIH Consensus Conference Criteria)
• Grade II-IV and III-IV acute GVHD per the NIH Consensus Conference Criteria on Acute GVHD Grading by Day +180
• Hematologic recovery including neutrophil engraftment, platelet engraftment, lymphocyte recovery
• Proportion of participants with full (at least 95% or more) or mixed (5.0-94.9%) total donor chimerism or graft rejection (less than 5% total donor chimerism)
• Graft failure
• Disease relapse or progression
• Non-relapse mortality (NRM)
• Toxicity and Infections
• Disease-free survival
• OS
• PRO