Clinical Trials Actively Recruiting

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.

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.

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.

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.

Phase 1b

Primary Objectives:

• To evaluate the safety and tolerability of AZD0120, and determine the RP2D of AZD0120 in participants with AL amyloidosis

Secondary Objectives:

• To evaluate the efficacy of AZD0120 in participants with AL amyloidosis
• To characterize the CK of AZD0120 in peripheral blood following a single-dose of AZD0120 in participants with AL amyloidosis
• To assess immunogenicity of AZD0120 in participants with AL amyloidosis

Phase 2

Primary Objectives:

• To evaluate the efficacy of AZD0120 in participants with AL amyloidosis

Secondary Objectives:

• To further evaluate the efficacy of AZD0120 in participants with AL amyloidosis
• To characterize the safety of AZD0120 in participants with AL amyloidosis
• To characterize the CK of AZD0120 in peripheral blood following a single-dose of AZD0120 in participants with AL amyloidosis
• To assess immunogenicity of AZD0120 in participants with AL amyloidosis
• To assess the effect of AZD0120 on overall health status in participants with AL amyloidosis

Primary Objectives:

• To evaluate the efficacy of BGB-16673 compared to pirtobrutinib as measured by progression-free survival (PFS) determined by independent review committee (IRC)

Secondary Objectives:

• To evaluate the efficacy of BGB-16673 compared to pirtobrutinib, as measured by overall survival (OS)
• To further evaluate the efficacy of BGB-16673 compared to pirtobrutinib, as measured by additional efficacy endpoints
• To evaluate the safety of BGB-16673 versus pirtobrutinib
• To evaluate patient-reported disease and treatment-specific symptoms and functioning in patients receiving BGB-16673 versus pirtobrutinib

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.

Primary Objectives:

• To compare the PFS of a standard chemotherapy approach versus an IO therapy approach (brentuximab vedotin and nivolumab) in patients with newly diagnosed early stage cHL who have a rapid early response (RER) as determined by PET2 after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy.
• To compare the PFS of a standard chemotherapy approach versus an IO therapy approach (brentuximab vedotin and nivolumab) plus involved site radiation therapy (ISRT) in patients with newly diagnosed early stage cHL who have a slow early response (SER) as determined by PET2 after 2 cycles of ABVD chemotherapy.

Secondary Objectives:

• To demonstrate non-inferiority of overall survival (OS) at 12 years of IO therapy versus standard therapy in early stage cHL patients who have a RER as determined by PET2 after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy.
• To evaluate the overall survival (OS) at 12 years of IO therapy versus standard therapy in early stage cHL patients who have a SER as determined by PET2 after 2 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy.
• To demonstrate non-inferiority of overall survival (OS) at 12 years of IO therapy versus standard therapy in early stage cHL patients.
• To evaluate in patients with newly diagnosed early stage cHL the PFS of a standard chemotherapy approach versus an IO therapy approach (brentuximab vedotin and nivolumab) in the overall cohort, in the favorable risk cohort, and in the unfavorable risk cohort.
• To evaluate the EFS at 12 years of patients undergoing standard chemotherapy versus an IO therapy approach (brentuximab vedotin and nivolumab). 1.2.6 To compare the physician-reported treatment-related adverse event (AE) rates between a standard chemotherapy approach and an IO therapy approach (brentuximab vedotin and nivolumab) in patients with newly diagnosed early stage cHL.
• To compare patient-reported adverse events using pediatric and adult versions of Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), stratified by age groups, therapeutic arms, and receipt of RT over time.
• To evaluate changes in patient-reported fatigue, cognitive functioning, and health-related quality of life (HRQoL), e.g., emotional, physical, and role functioning, by treatment arm, using validated adult and pediatric measurement systems.
• To evaluate self-reported late morbidities (e.g., cardiovascular, pulmonary and endocrine) over time for children, adolescents and adults undergoing standard chemotherapy versus an IO therapy approach (brentuximab vedotin and nivolumab) with and without RT using measures from the St. Jude Lifetime Cohort Study (SJLIFE).
• To evaluate FDG-PET measurements of metabolic tumor burden (MTV and TLG) at PET1 as a predictive marker of PFS. 1.2.11 To evaluate the associations between race/ethnicity and key outcomes including early response to therapy, PFS and OS.

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.

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.