Clinical Trials Actively Recruiting

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:

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 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.

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 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

Objective:

Primary Objectives:

• Screening and Reassessment (MSRP): To evaluate the feasibility of MATCHBox receiving and organizing all data needed for assignment to a myeloMATCH clinica >trial or Tier Advancement Pathway (TAP) within 72 hours of MDNet receipt of al >required specimens for initial therapy and within 10 days for subsequent therapy.
• Tier Advancement Pathway (TAP): To enable participants who are not matched to an investigational myeloMATCH treatment substudy to receive standard of care (SOC) while remaining on the MSRP to maintain access to later tiers of treatment substudies.

Secondary Objectives:

• Screening and Reassessment (MSRP)
  • To describe the time to generation of all data required for treatment substudy (or TAP) assignment, time to treatment substudy (or TAP) assignment, percent assigned to a myeloMATCH treatment substudy, and the percent of screened participants who register to a myeloMATCH investigational treatment substudy or are assigned to TAP:
    • Separately within each tier of myeloMATCH treatment substudy and analogous TAP assignment (see Section 2.1 for tier definitions)
    • Separately within each clinical basket of myeloMATCH treatment substudies (see Section 2.2 for clinical basket definitions).
    • Over time, across and within the categories above.
• Tier Advancement Pathway (TAP)
  • To evaluate participants for assignment to higher tier treatment substudies within myeloMATCH.
  • To describe, within tier- and basket- levels of TAP, measurable residual disease (MRD) rates and clonal evolution.
  • To describe, within tier- and basket- levels of TAP, remission status and overall survival of participants who receive standard of care therapy.
  • To obtain MDNet specimens for translational medicine and biobanking.

Objective:

Phase 1

Primary Objectives:

• Part 1 (Dose Escalation): Determine the RP2D(s) of bleximenib
• Part 2 (Dose Expansion): Determine safety and tolerability at the RP2D(s)

Secondary Objectives:

• Assess pharmacokinetics
• Assess preliminary clinical activity

Phase 2

Primary Objectives:

• To evaluate the efficacy of bleximenib at the RP2D

Secondary Objectives:

• To further assess the efficacy of bleximenib at the RP2D
• To evaluate MRD rate at the RP2D
• To assess the safety and tolerability of bleximenib at the RP2D
• To assess the effect of bleximenib on transfusion requirements
• To characterize PK of bleximenib at the RP2D
• To assess PROs with bleximenib at the RP2D