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

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ClinicalTrials.gov Identifier: NCT04735471
Recruitment Status : Recruiting
First Posted : February 3, 2021
Last Update Posted : June 4, 2021
Sponsor:
Information provided by (Responsible Party):
Adicet Bio, Inc

Brief Summary:

The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies. Study details include:

Study Duration: 2 years (1 year of enrollment and 1 year of study participation) Treatment Duration: ADI-001:1 day (single dose); IL-2 (Part 3 only): 14 days Visit Frequency: Daily for 8 days, then Day 10, 12, 14, 21, 28, and Month 3, 6, 9, and 12


Condition or disease Intervention/treatment Phase
Lymphoma, Follicular Lymphoma, Mantle-Cell Marginal Zone Lymphoma Lymphoma, Burkitt Mediastinal Lymphoma Diffuse Large B Cell Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Large B-Cell, Diffuse Genetic: ADI-001 Drug: Fludarabine Drug: Cyclophosphamide Drug: Bendamustine Drug: Interleukin-2 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 optimal dose. Patients will be administered a single infusion of ADI-001 cells. A combination of ADI-001 and interleukin (IL)-2 may also be evaluated after the MTD or optimal dose has been determined for the single agent.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 3+3 Factorial 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 T Cells in Adults With B Cell Malignancies, in Monotherapy and Combination With IL 2
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 to determine the maximum tolerated dose (MTD) or optimal ADI-001 dose (Part 1).
Genetic: ADI-001
Anti-CD20 CAR-T

Drug: Fludarabine
Chemotherapy for Lymphodepletion

Drug: Cyclophosphamide
Chemotherapy for Lymphodepletion

Drug: Bendamustine
Chemotherapy for Lymphodepletion

Experimental: ADI-001 Dose Expansion
ADI-001 is administered via infusion to 3 NHL subtypes to confirm dose (Part 2).
Genetic: ADI-001
Anti-CD20 CAR-T

Drug: Fludarabine
Chemotherapy for Lymphodepletion

Drug: Cyclophosphamide
Chemotherapy for Lymphodepletion

Drug: Bendamustine
Chemotherapy for Lymphodepletion

Experimental: ADI-001 in combination with Interleukin-2
ADI-001 is administered via infusion in combination with subcutaneously administered IL-2 (Part 3).
Genetic: ADI-001
Anti-CD20 CAR-T

Drug: Fludarabine
Chemotherapy for Lymphodepletion

Drug: Cyclophosphamide
Chemotherapy for Lymphodepletion

Drug: Bendamustine
Chemotherapy for Lymphodepletion

Drug: Interleukin-2
To support growth and activation of ADI-001




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 optimal dose.

  2. Proportion of treatment emergent and treatment related adverse events [ Time Frame: 1 year ]
    This primary endpoint will be used to determine the optimal dose of ADI-001


Secondary Outcome Measures :
  1. Duration of ADI-001 persistence [ 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 by Lugano Criteria [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  4. Progression Free Survival by Lugano Criteria [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  5. Time To Progression by Lugano Criteria [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
  6. Overall Survival by Lugano Criteria [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]


Information from the National Library of Medicine

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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.
  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. Resolved toxicities of any prior therapy to either baseline or CTCAE grade 1 (version 5.0)
  8. Female patients who are not pregnant or breastfeeding
  9. 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. Known CD20-negative B cell lymphoma at time of initial diagnosis
  2. 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])
  3. 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
  4. History of any clinically significant conditions in the opinion of the Investigator, including, but not limited to:

    1. Infection (including sepsis, pneumonia, bacteremia, fungal, viral and opportunistic infections) within 4 weeks prior to first dose of ADI 001
    2. Any form of primary immunodeficiency such as severe combined immunodeficiency disease
    3. Cardiovascular conditions (Class III or IV heart failure as defined by the New York Heart Association [NYHA], cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease) within the past 6 months
    4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura within the 4 weeks prior to first dose of ADI 001 or the need for daily prednisone greater than 5 mg (or corticosteroid equivalent) to control an autoimmune disease
    5. Severe immediate hypersensitivity reaction to any of the agents used in this study
  5. 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. Exception: Prior therapy with approved anti-CD19 CAR T cell products is allowed.

    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 stem cell transplant and donor lymphocyte infusion within 3 months of planned CAR T cell infusion

  6. 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: Peg Taylor (650) 850-8020 clinicaltrials@adicetbio.com

Locations
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United States, California
Stanford University Medical Centr 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 Not yet recruiting
Dallas, Texas, United States, 75204
Contact: Houston Holmes, MD         
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
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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 4, 2021
Last Verified: June 2021
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:
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Bendamustine
Fludarabine
Interleukin-2
T cells,gamma delta
Immunotherapy, Adoptive
Antigens, CD20
Additional relevant MeSH terms:
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Burkitt Lymphoma
Lymphoma
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
Lymphoma, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Cyclophosphamide
Bendamustine Hydrochloride
Fludarabine
Interleukin-2
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents