Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma
Conditions
Keywords
CAR T, Cell Therapy, Allogeneic Cell Therapy, Cellular Immuno-therapy, AlloCAR T, ALLO-501A, ALLO-647, LBCL, Lymphoma, Large B-Cell Lymphoma, Cema-cel, Cemacabtagene ansegedleucel, Leukemia, Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL
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.
Interventions
Sponsors
Allogene Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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: 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: 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: Overall Survival (OS) | Up to 60 months | OS, defined as the time from the enrollment date to death |
| Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count | Up to 9 months | — |
| 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: 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 | — |
| 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: 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: 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: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647 | Up to 60 months | — |
Countries
Australia, Canada, United States
Outcome results
None listed