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

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

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Marginal Zone Lymphoma; Diffuse Large B Cell Lymphoma; Primary Mediastinal B-cell Lymphoma
• Intervention / Treatment: Genetic: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami- Sylvester Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital Blood and Marrow Transplant Group of Georgia
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The State University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75204
      • Baylor Scott & White Research Institute
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort	This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).	Day 28
Proportion of treatment emergent and treatment related adverse events	This primary endpoint will be used to determine the MTD/MAD of ADI-001	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and persistence of ADI-001	Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood	Day 1 through Month 12
Overall Response Rate by Lugano Criteria		Day 28, Month 3, 6, 9, and 12
Duration of Response		Day 28, Month 3, 6, 9, and 12
Progression Free Survival		Day 28, Month 3, 6, 9, and 12
Time To Progression		Day 28, Month 3, 6, 9, and 12
Overall Survival		Day 28, Month 3, 6, 9, and 12

Collaborators and Investigators

• Sponsor: Adicet Therapeutics
• Investigators: Study Director: Adicet Medical Director, Adicet Bio

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Actual): February 3, 2025
• Study Completion (Actual): February 3, 2025

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 28, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Cell Therapy; CAR-T; B-cell lymphoma; Allogeneic Cell Therapy; T cells, gamma delta; Immunotherapy, Adoptive; Antigens, CD20
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: ADI-20200101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No