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)

Phase 2Active Not RecruitingNCT04416984

Allogene Therapeutics160 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

160

Conditions

Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (23)

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

...and 13 more locations

Outcomes

Primary Outcomes

Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A

Dose limiting toxicity is defined as protocol-defined ALLO-501A-related adverse events with onset within 28 days following infusion

Time frame: 28 days

Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A

DLT is defined as protocol-defined ALLO-647-related adverse events with onset within 33 days following 1st infusion

Time frame: 33 days

Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest

Time frame: Up to 60 months

Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC)

ORR defined as assessment of CR and PR using Lugano classification criteria 2014

Time frame: Up to 60 months

Secondary Outcomes

Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator

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)

Time frame: Up to 60 months

Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator

Time frame: 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

CR Complete Response, PR Partial Response, SD Stable Disease, PD Progressive Disease

Time frame: Up to 60 months

Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator

PFS, defined as time from the enrollment date to progression, relapse, or death

Time frame: Up to 60 months

Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator

TTR, defined as the time from the enrollment date to the first observed response

Time frame: Up to 60 months

Phase 1a, 1b, and 2: Overall Survival (OS)

OS, defined as the time from the enrollment date to death

Time frame: Up to 60 months

Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count

Time frame: Up to 9 months

Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery

Time frame: 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

Time frame: Up to 9 months

Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)

Time frame: Up to 9 months

Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)

Time frame: Up to 9 months

Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)

Time frame: Up to 9 months

Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)

Time frame: Up to 9 months

Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts

Time frame: Up to 9 months

Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®

Time frame: Up to 9 months

Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647

Time frame: 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

The incidence and severity of Cytokine Release Syndrome (CRS), Graft-Versus-Host Disease (GVHD), infections, cytopenias, and neurotoxicity

Time frame: Up to 60 months

Phase 1a, 1b, and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647

The incidence of infusion-related reactions, cytopenias, and infections

Time frame: Up to 60 months

Phase 1a, 1b, and 2: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647

Time frame: Up to 60 months