Clinical trial NCT04416984: 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)
Official title: A Single-Arm, Open-Label, Phase 1/2 Study Evaluating the Safety, Efficacy, and Cellular Kinetics/Pharmacodynamics of ALLO-501A, an Anti-CD19 Allogeneic CAR T Cell Therapy, and ALLO-647, an Anti-CD52 Monoclonal Antibody, in Subjects with Relapsed/Refractory Large B-Cell Lymphoma (LBCL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma
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
Lead sponsor: Allogene Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-06-04
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A
timeFrame: 28 days
measure: Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A
timeFrame: 33 days
measure: Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest
timeFrame: Up to 60 months
measure: Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC)
timeFrame: Up to 60 months
Secondary outcomes:
measure: Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: Overall Survival (OS)
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: Serum concentration of ALLO-647 as measured by microgram per microliter for use in a population PK model
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647
timeFrame: Up to 9 months
measure: Phase 1a, 1b, and 2: Adverse Events (AEs) as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647
timeFrame: Up to 60 months
measure: Phase 1a, 1b, and 2: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital - Atlanta
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: St. David's South Austin Medical Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center - University of Texas
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Halifax
country: Canada
facility: QEII Health Sciences Centre-VG Site
state: Nova Scotia
city: Québec
country: Canada
facility: CHU de Québec -Université Laval; Hôpital de l'Enfant-Jésus
state: Quebec
Study officials:
References: