A Safety and Efficacy Study of ADI-001, an Anti-CD20 Allogeneic Gamma Delta CAR-T, in Subjects With B Cell Malignancies (GLEAN-1)
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| ClinicalTrials.gov Identifier: NCT04735471 |
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Recruitment Status :
Recruiting
First Posted : February 3, 2021
Last Update Posted : March 13, 2023
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| 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 |
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 (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 |
|---|---|
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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).
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Genetic: ADI-001
Anti-CD20 CAR-T Drug: Fludarabine Chemotherapy for Lymphodepletion Drug: Cyclophosphamide Chemotherapy for Lymphodepletion |
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Experimental: ADI-001 Dose Extension
ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
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Genetic: ADI-001
Anti-CD20 CAR-T Drug: Fludarabine Chemotherapy for Lymphodepletion Drug: Cyclophosphamide Chemotherapy for Lymphodepletion |
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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).
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Genetic: ADI-001
Anti-CD20 CAR-T Drug: Fludarabine Chemotherapy for Lymphodepletion Drug: Cyclophosphamide Chemotherapy for Lymphodepletion |
- 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).
- 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
- 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
- Overall Response Rate by Lugano Criteria [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
- Duration of Response [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
- Progression Free Survival [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
- Time To Progression [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
- Overall Survival [ Time Frame: Day 28, Month 3, 6, 9, and 12 ]
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Relapsed/refractory (R/R) previously treated B cell malignancies.
- Prior treatment must include at least 2 prior regimens, including anti CD20 antibody therapies. Prior Treatment with CD19 CAR T may be considered.
- Documented measurable disease as defined by Lugano 2014
- Male or female ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1
- Adequate hematological, renal, pulmonary, cardiac, and liver function
- Female patients who are not pregnant or breastfeeding
- 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:
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Current or history of any of the following conditions:
- Central nervous system (CNS) primary lymphoma (current or history)
- Unrelated malignancy requiring systemic treatment (current or history [in the past 3 years, other than hormonal treatment which is allowed])
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Any of the following current conditions:
- 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
- Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration
- Tumor mass effects such as bowel obstruction or blood vessel compression that require therapy
- Opportunistic infections
- History of any clinically significant conditions in the opinion of the Investigator
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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
- Patients unwilling to participate in an extended safety monitoring period (long term follow up [LTFU] protocol)
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
| Contact: Rose Lai, MD | 6263181179 | clinicaltrials@adicetbio.com |
| 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, Florida | |
| University of Miami- Sylvester Comprehensive Cancer Center | Recruiting |
| Miami, Florida, United States, 33136 | |
| Contact: Jay Spiegel, MD spiegelj@med.miami.edu | |
| United States, Georgia | |
| Northside Hospital Blood and Marrow Transplant Group of Georgia | Recruiting |
| Atlanta, Georgia, United States, 30342 | |
| Contact: Asad Bashey, MD abashey@btmga.com | |
| United States, Iowa | |
| The State University of Iowa | Recruiting |
| Iowa City, Iowa, United States, 52242 | |
| Contact: Umar Farooq, MD umar-farooq@uiowa.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 SNeelapu@mdanderson.org | |
| United States, Wisconsin | |
| Medical College of Wisconsin | Recruiting |
| Milwaukee, Wisconsin, United States, 53226 | |
| Contact: Mehdi Hamadani, MD 414-805-0505 mhamadani@mcw.edu | |
| Study Director: | Rose Lai, MD | Adicet Bio |
| 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: | March 13, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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B-cell lymphoma CAR-T Cell Therapy Allogeneic Cell Therapy |
T cells, gamma delta Immunotherapy, Adoptive Antigens, CD20 |
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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 |