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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04416984




Registration number
NCT04416984
Ethics application status
Date submitted
29/05/2020
Date registered
4/06/2020
Date last updated
6/06/2024

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
ALLO-501A-201
Universal Trial Number (UTN)
Trial acronym
ALPHA2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Large B Cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - ALLO-501A
Treatment: Other - ALLO-647
Treatment: Drugs - Fludarabine
Treatment: Drugs - Cyclophosphamide

Experimental: ALLO-501A, ALLO-647 -


Treatment: Other: ALLO-501A
ALLO-501A is an allogeneic CAR T cell therapy targeting CD19

Treatment: Other: ALLO-647
ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen

Treatment: Drugs: Fludarabine
Chemotherapy for lymphodepletion

Treatment: Drugs: Cyclophosphamide
Chemotherapy for lymphodepletion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicities (DLT) at increasing doses of ALLO-501A
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Phase 1a: Proportion of subjects experiencing Dose Limiting Toxicity with ALLO-647 in combination with fludarabine/cyclophosphamide administered prior to ALLO-501A
Timepoint [2] 0 0
33 days
Primary outcome [3] 0 0
Phase 1b: Frequency and severity of ALLO-501A treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest
Timepoint [3] 0 0
Up to 60 months
Primary outcome [4] 0 0
Phase 2: Overall Response Rate (ORR) assessed per Independent Review Committee (IRC)
Timepoint [4] 0 0
Up to 60 months
Secondary outcome [1] 0 0
Phase 1a, 1b, and 2: Duration of Response (DOR) assessed per IRC (Phase 2 only) and per investigator
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [2] 0 0
Phase 1a, 1b, and 2: Overall Response Rate (ORR) assessed per investigator
Timepoint [2] 0 0
Up to 60 months
Secondary outcome [3] 0 0
Phase 1a, 1b, and 2: Best overall response (CR, PR, SD, PD) assessed per IRC (Phase 2 only) and per investigator
Timepoint [3] 0 0
Up to 60 months
Secondary outcome [4] 0 0
Phase 1a, 1b, and 2: Progression Free Survival (PFS) assessed per IRC (Phase 2 only) and per investigator
Timepoint [4] 0 0
Up to 60 months
Secondary outcome [5] 0 0
Phase 1a, 1b, and 2: Time to Response (TTR) assessed per IRC (Phase 2 only) and per investigator
Timepoint [5] 0 0
Up to 60 months
Secondary outcome [6] 0 0
Phase 1a, 1b, and 2: Overall Survival (OS)
Timepoint [6] 0 0
Up to 60 months
Secondary outcome [7] 0 0
Phase 1a, 1b, and 2: Depth of lymphodepletion as assessed by lymphocyte count
Timepoint [7] 0 0
Up to 9 months
Secondary outcome [8] 0 0
Phase 1a, 1b, and 2: Duration of lymphodepletion as assessed by lymphocyte recovery
Timepoint [8] 0 0
Up to 9 months
Secondary outcome [9] 0 0
Phase 1a, 1b, and 2: Serum concentration of ALLO-647 as measured by microgram per microliter for use in a population PK model
Timepoint [9] 0 0
Up to 9 months
Secondary outcome [10] 0 0
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by peak blood concentration (Cmax)
Timepoint [10] 0 0
Up to 9 months
Secondary outcome [11] 0 0
Phase 1a, 1b, and 2: ALLO-501A expansion assessed by area under the curve (AUC)
Timepoint [11] 0 0
Up to 9 months
Secondary outcome [12] 0 0
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by peak blood concentration (Cmax)
Timepoint [12] 0 0
Up to 9 months
Secondary outcome [13] 0 0
Phase 1a, 1b, and 2: ALLO-501A persistence assessed by area under the curve (AUC)
Timepoint [13] 0 0
Up to 9 months
Secondary outcome [14] 0 0
Phase 1a, 1b, and 2: Pharmacodynamics will be evaluated on host T cell counts
Timepoint [14] 0 0
Up to 9 months
Secondary outcome [15] 0 0
Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-501A scFv and/or TALEN®
Timepoint [15] 0 0
Up to 9 months
Secondary outcome [16] 0 0
Phase 1a, 1b, and 2: The incidence of anti-drug antibodies against ALLO-647
Timepoint [16] 0 0
Up to 9 months
Secondary outcome [17] 0 0
Phase 1a, 1b, and 2: Adverse Events (AEs) as characterized by preferred term, frequency, severity timing, seriousness, and relationship to ALLO-501A
Timepoint [17] 0 0
Up to 60 months
Secondary outcome [18] 0 0
Phase 1a, 1b, and 2: AEs as characterized by preferred term, frequency, severity, timing, seriousness, and relationship to ALLO-647
Timepoint [18] 0 0
Up to 60 months
Secondary outcome [19] 0 0
Phase 1a, 1b, and 2: The incidence and severity of clinically significant laboratory toxicities and relationship to ALLO-647
Timepoint [19] 0 0
Up to 60 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/05/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2029
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Dakota
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Canada
State/province [17] 0 0
British Columbia
Country [18] 0 0
Canada
State/province [18] 0 0
Nova Scotia
Country [19] 0 0
Canada
State/province [19] 0 0
Québec
Country [20] 0 0
Italy
State/province [20] 0 0
Bologna
Country [21] 0 0
Italy
State/province [21] 0 0
Milan
Country [22] 0 0
Italy
State/province [22] 0 0
Torino
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Donostia-San Sebastian
Country [25] 0 0
Spain
State/province [25] 0 0
Madrid
Country [26] 0 0
Spain
State/province [26] 0 0
Salamanca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Allogene Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04416984
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Allogene Therapeutics Inc.
Address 0 0
Country 0 0
Phone 0 0
415-604-5696
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04416984