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

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04735471
Recruitment Status : Recruiting
First Posted : February 3, 2021
Last Update Posted : June 9, 2022
Sponsor:
Information provided by (Responsible Party):
Adicet Bio, Inc

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+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 : March 4, 2021
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2024


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




Primary Outcome Measures :
  1. The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  3. Duration of Response [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  4. Progression Free Survival [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  5. Time To Progression [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  6. Overall Survival [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04735471


Contacts
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Contact: Rose Lai, MD 6263181179 clinicaltrials@adicetbio.com

Locations
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United States, California
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: David Miklos, MD    650-723-0822    dmiklos@stanford.edu   
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
Contact: Don A Stevens, MD    502-899-3366    Don.Stevens@nortonhealthcare.org   
United States, Texas
Baylor Scott & White Research Institute Recruiting
Dallas, Texas, United States, 75204
Contact: Houston Holmes, MD    214-370-1000    houston.holmes@usoncology.com   
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sattva Neelapu, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Mehdi Hamadani, MD    414-805-0505    mhamadani@mcw.edu   
Sponsors and Collaborators
Adicet Bio, Inc
Investigators
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Study Director: Rose Lai, MD Adicet Bio
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Adicet Bio, Inc
ClinicalTrials.gov Identifier: NCT04735471    
Other Study ID Numbers: ADI-20200101
First Posted: February 3, 2021    Key Record Dates
Last Update Posted: June 9, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists