A Phase 1 Study of ADI-001 in B Cell Malignancies

NCT ID: NCT04735471

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-04
• Study Completion Date: 2025-02-03

Brief Summary

This is a Phase 1 dose escalation 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.

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.

Conditions

Lymphoma, Follicular; Lymphoma, Mantle-Cell; Marginal Zone Lymphoma; Primary Mediastinal B-cell Lymphoma; Diffuse Large B Cell Lymphoma; Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

ADI-001

Intervention Type: GENETIC

Anti-CD20 CAR-T

Fludarabine

Intervention Type: DRUG

Chemotherapy for Lymphodepletion

Cyclophosphamide

Intervention Type: DRUG

Chemotherapy for Lymphodepletion

ADI-001 Dose Extension

ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).

Group Type: EXPERIMENTAL

ADI-001

Intervention Type: GENETIC

Anti-CD20 CAR-T

Fludarabine

Intervention Type: DRUG

Chemotherapy for Lymphodepletion

Cyclophosphamide

Intervention Type: DRUG

Chemotherapy for Lymphodepletion

ADI-001 Dose Expansion

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Group Type: EXPERIMENTAL

ADI-001

Intervention Type: GENETIC

Anti-CD20 CAR-T

Fludarabine

Intervention Type: DRUG

Chemotherapy for Lymphodepletion

Cyclophosphamide

Intervention Type: DRUG

Chemotherapy for Lymphodepletion

Interventions

ADI-001

Anti-CD20 CAR-T

Intervention Type: GENETIC

Fludarabine

Chemotherapy for Lymphodepletion

Intervention Type: DRUG

Cyclophosphamide

Chemotherapy for Lymphodepletion

Intervention Type: DRUG

Eligibility Criteria

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:

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

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

2. Any of the following current conditions:

1. 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

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

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

4. Opportunistic infections

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

4. 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Adicet Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adicet Medical Director

Role: STUDY_DIRECTOR

Adicet Bio

Locations

Stanford University Medical Center

Stanford, California, United States

University of Miami- Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Northside Hospital Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

The State University of Iowa

Iowa City, Iowa, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Baylor Scott & White Research Institute

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Swedish Cancer Center

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Nishimoto KP, Barca T, Azameera A, Makkouk A, Romero JM, Bai L, Brodey MM, Kennedy-Wilde J, Shao H, Papaioannou S, Doan A, Masri C, Hoang NT, Tessman H, Ramanathan VD, Giner-Rubio A, Delfino F, Sharma K, Bray K, Hoopes M, Satpayev D, Sengupta R, Herrman M, Abbot SE, Aftab BT, An Z, Panuganti S, Hayes SM. Allogeneic CD20-targeted gammadelta T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models. Clin Transl Immunology. 2022 Feb 2;11(2):e1373. doi: 10.1002/cti2.1373. eCollection 2022.

Reference Type: DERIVED

PMID: 35136603 (View on PubMed)

Other Identifiers

ADI-20200101

Identifier Type: -

Identifier Source: org_study_id