GLEAN-1: A Safety and Efficacy Study of ADI-001, an Anti-CD20 Allogeneic Gamma Delta CAR-T, in Subjects With B Cell Malignancies

• Sponsor: Adicet Bio, Inc (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04735471
• Collaborator: (none)
• Enrollment: 78
• Locations: 5
• Arms: 3
• Anticipated Duration (Months): 36.9
• Patients Per Site: 15.6
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a Phase 1 dose esclation study following a 3+3 study design. The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Follicular; Lymphoma, Mantle-Cell; Marginal Zone Lymphoma; Primary Mediastinal B-cell Lymphoma; Diffuse Large B Cell Lymphoma; Lymphoma, Non-Hodgkin	Genetic: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide	Phase 1

Detailed Description

ADI-001 is an investigational immunotherapy composed of allogeneic gamma delta T cells that is being evaluated as a potential treatment for patients diagnosed with B cell malignancies who have relapsed or are refractory to at least two prior regimens. This first-in-human study will assess the safety and tolerability of ADI-001 and is designed to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Patients will be administered a single infusion or multiple infusions of ADI-001 cells. The study will include the following two parts:

Part 1 : dose escalation and extension. Parts 1a (escalation) and 1b (extension) will involve escalation and administration of single dose of ADI-001 and multiple doses of ADI-001.

Part 2 : dose expansion will involve dose administration of ADI-001 at MTD/MAD as determined in Part 1.

The study will also assess the pharmacokinetics and pharmacodynamics of ADI-001.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 78 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 3+3 Dose Escalation Design3+3 Dose Escalation Design
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Safety and Efficacy Study of ADI-001 Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T Cells in Adults With B Cell Malignancies
• Actual Study Start Date: Mar 4, 2021
• Anticipated Primary Completion Date: Mar 31, 2023
• Anticipated Study Completion Date: Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ADI-001 Dose Escalation ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).	Genetic: ADI-001; Anti-CD20 CAR-T; Drug: Fludarabine; Chemotherapy for Lymphodepletion; Drug: Cyclophosphamide; Chemotherapy for Lymphodepletion
Experimental: ADI-001 Dose Extension ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).	Genetic: ADI-001; Anti-CD20 CAR-T; Drug: Fludarabine; Chemotherapy for Lymphodepletion; Drug: Cyclophosphamide; Chemotherapy for Lymphodepletion
Experimental: ADI-001 Dose Expansion Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).	Genetic: ADI-001; Anti-CD20 CAR-T; Drug: Fludarabine; Chemotherapy for Lymphodepletion; Drug: Cyclophosphamide; Chemotherapy for Lymphodepletion

Outcome Measures

Primary Outcome Measures

1. The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort [Day 28]

   This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).

2. Proportion of treatment emergent and treatment related adverse events [1 year]

   This primary endpoint will be used to determine the MTD/MAD of ADI-001

Secondary Outcome Measures

1. Frequency and persistence of ADI-001 [Day 1 through Month 12]

   Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood

2. Overall Response Rate by Lugano Criteria [Day 28, Month 3, 6, 9, and 12]

3. Duration of Response [Day 28, Month 3, 6, 9, and 12]

4. Progression Free Survival [Day 28, Month 3, 6, 9, and 12]

5. Time To Progression [Day 28, Month 3, 6, 9, and 12]

6. Overall Survival [Day 28, Month 3, 6, 9, and 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Relapsed/refractory (R/R) previously treated B cell malignancies.

2. Prior treatment must include at least 2 prior regimens, including anti CD20 antibody therapies. Prior Treatment with CD19 CAR T may be considered.

3. Documented measurable disease as defined by Lugano 2014

4. Male or female ≥ 18 years of age

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1

6. Adequate hematological, renal, pulmonary, cardiac, and liver function

7. Female patients who are not pregnant or breastfeeding

8. Female patients of childbearing potential and all male patients must agree to use highly effective methods of birth control for the duration of the study.

Exclusion Criteria:

1. Current or history of any of the following conditions:

2. Central nervous system (CNS) primary lymphoma (current or history)

3. Unrelated malignancy requiring systemic treatment (current or history [in the past 3 years, other than hormonal treatment which is allowed])

4. Any of the following current conditions:

5. Active acute or chronic graft versus host disease (GvHD) other than grade 1 with skin involvement, or GvHD requiring immunosuppressive treatment within 4 weeks of enrollment

6. Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration

7. Tumor mass effects such as bowel obstruction or blood vessel compression that require therapy

8. Opportunistic infections

9. History of any clinically significant conditions in the opinion of the Investigator

10. Prior treatment with any of the following:

a Gene therapy, genetically modified cell therapy, or adoptive T cell therapy within 6 weeks of study enrollment.

b Radiation therapy within 4 weeks prior to study entry. Palliative local radiation may be allowed within 1 week prior to study entry.

c Autologous stem cell transplant (SCT) within 6 weeks of planned ADI 001 infusion d Allogeneic transplant and donor lymphocyte infusion within 3 months of planned CAR T cell infusion

1. Patients unwilling to participate in an extended safety monitoring period (long term follow up [LTFU] protocol)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University Medical Center	Stanford	California	United States	94305
2	Norton Cancer Institute	Louisville	Kentucky	United States	40207
3	Baylor Scott & White Research Institute	Dallas	Texas	United States	75204
4	MD Anderson Cancer Center	Houston	Texas	United States	77030
5	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Adicet Bio, Inc

Investigators

• Study Director: Rose Lai, MD, Adicet Bio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Adicet Bio, Inc
• ClinicalTrials.gov Identifier: NCT04735471
• Other Study ID Numbers: ADI-20200101
• First Posted: Feb 3, 2021
• Last Update Posted: Jun 9, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Adicet Bio, Inc: B-cell lymphoma; CAR-T; Cell Therapy; Allogeneic Cell Therapy; T cells, gamma delta; Immunotherapy, Adoptive; Antigens, CD20
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Cyclophosphamide; Fludarabine

Study Results

No Results Posted as of Jun 9, 2022