Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
NA
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04416984