Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults with Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2)
- Conditions
- Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma
- Interventions
- Registration Number
- NCT04416984
- Lead Sponsor
- Allogene Therapeutics
- Brief Summary
This is a single-arm, open label, multicenter Phase 1/2 study evaluating ALLO-501A in adult subjects with R/R LBCL and CLL/SLL. The purpose of the ALPHA2 study is to assess the safety, efficacy, and cell kinetics of ALLO-501A in adults with relapsed or refractory large B-cell lymphoma and assess the safety of ALLO-501A in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after a lymphodepletion regimen comprising fludarabine, cyclophosphamide, and ALLO-647.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 160
For subjects with LBCL:
- Histologically confirmed diagnosis of relapsed/refractory large B-cell lymphoma at last relapse per WHO 2017
- At least 1 measurable lesion at time of enrollment
- Relapsed or refractory disease after at least 2 lines of chemotherapy
- Absence of significant donor (product)-specific anti-HLA antibodies (DSA) at screening (Note: Only applicable for Phase 2)
For subjects with CLL/SLL:
- Diagnosis of CLL/SLL
- Relapsed/refractory disease
- Subjects relapsed/refractory to BTKi therapy and high-risk disease
- Subjects relapsed/refractory with 2 or more lines of therapy including BTKi and BCL-2 inhibitor (venetoclax)
- At least 1 measurable lesion at time of enrollment
For all subjects:
- Male or female subjects ≥18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Adequate hematological, renal, and liver function
- Active central nervous system (CNS) involvement by malignancy
- Current thyroid disorder (including hyperthyroidism), except for subjects with hypothyroidism controlled on a stable dose of hormone replacement therapy
- Any other active malignancies that required systemic treatment within 3 years prior to enrollment
- Radiation therapy within 2 weeks prior to ALLO-647
- Prior irradiation to >25% of the bone marrow
- Hypocellular bone marrow for age by institutional standard as determined from a bone marrow biopsy performed at time of screening (Note: Only applicable for Phase 2).
- Autologous hematopoietic stem cell transplant (HSCT) within last 6 months (24 weeks)
- Systemic anti-cancer therapy within 2 weeks prior to receiving ALLO-647
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ALLO-501A, ALLO-647 ALLO-501A - ALLO-501A, ALLO-647 ALLO-647 - ALLO-501A, ALLO-647 Fludarabine - ALLO-501A, ALLO-647 Cyclophosphamide -
- Primary Outcome Measures
Name Time Method Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A 28 days Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion
Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A 33 days DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion
Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest Up to 60 months Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC) Up to 60 months ORR defined as assessment of CR and PR using Lugano classification criteria 2014
- Secondary Outcome Measures
Name Time Method Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator Up to 60 months DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression or death, whichever comes first per (Cheson et al, 2014)
Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator Up to 60 months PFS, defined as time from the enrollment date to progression, relapse, or death
Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count Up to 9 months Phase 1a, 1b, and 2: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647 Up to 60 months Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator Up to 60 months Phase 1a, 1b, and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator Up to 60 months CR Complete Response, PR Partial Response, SD Stable Disease, PD Progressive Disease
Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery Up to 9 months Phase 1a, 1b, and 2: Serum concentration of ALLO-647 as measured by microgram per microliter for use in a population PK model Up to 9 months Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN® Up to 9 months Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647 Up to 9 months Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator Up to 60 months TTR, defined as the time from the enrollment date to the first observed response
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax) Up to 9 months Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC) Up to 9 months Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts Up to 9 months Phase 1a, 1b, and 2: Adverse Events (AEs) as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A Up to 60 months The incidence and severity of Cytokine Release Syndrome (CRS), Graft-Versus-Host Disease (GVHD), infections, cytopenias, and neurotoxicity
Phase 1a, 1b, and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647 Up to 60 months The incidence of infusion-related reactions, cytopenias, and infections
Phase 1a, 1b, and 2: Overall Survival (OS) Up to 60 months OS, defined as the time from the enrollment date to death
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax) Up to 9 months Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC) Up to 9 months
Trial Locations
- Locations (23)
QEII Health Sciences Centre-VG Site
🇨🇦Halifax, Nova Scotia, Canada
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
City of Hope
🇺🇸Duarte, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
Advent Health
🇺🇸Orlando, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Northside Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
St. David's South Austin Medical Center
🇺🇸Austin, Texas, United States
Texas Oncology
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center - University of Texas
🇺🇸Houston, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
St. Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
CHU de Québec -Université Laval; Hôpital de l'Enfant-Jésus
🇨🇦Québec, Quebec, Canada