Description:
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
Title
- Brief Title: A Study of ADI-001 in B Cell Malignancies
- 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
Clinical Trial IDs
- ORG STUDY ID:
ADI-20200101
- NCT ID:
NCT04735471
Conditions
- 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
Interventions
Drug | Synonyms | Arms |
---|
Fludarabine | | ADI-001 Dose Escalation |
Cyclophosphamide | | ADI-001 Dose Escalation |
Bendamustine | | ADI-001 Dose Escalation |
Interleukin-2 | | ADI-001 in combination with Interleukin-2 |
Purpose
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
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.
Trial Arms
Name | Type | Description | Interventions |
---|
ADI-001 Dose Escalation | Experimental | ADI-001 is administered via infusion with ascending dose levels to determine the maximum tolerated dose (MTD) or optimal ADI-001 dose (Part 1). | - Fludarabine
- Cyclophosphamide
- Bendamustine
|
ADI-001 Dose Expansion | Experimental | ADI-001 is administered via infusion to 3 NHL subtypes to confirm dose (Part 2). | - Fludarabine
- Cyclophosphamide
- Bendamustine
|
ADI-001 in combination with Interleukin-2 | Experimental | ADI-001 is administered via infusion in combination with subcutaneously administered IL-2 (Part 3). | - Fludarabine
- Cyclophosphamide
- Bendamustine
- Interleukin-2
|
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.
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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort |
Time Frame: | Day 28 |
Safety Issue: | |
Description: | This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or optimal dose. |
Secondary Outcome Measures
Measure: | Duration of ADI-001 persistence |
Time Frame: | Day 1 through Month 12 |
Safety Issue: | |
Description: | Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood |
Measure: | Overall Response Rate by Lugano Criteria |
Time Frame: | Day 28, Month 3, 6, 9, and 12 |
Safety Issue: | |
Description: | |
Measure: | Duration of Response by Lugano Criteria |
Time Frame: | Day 28, Month 3, 6, 9, and 12 |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival by Lugano Criteria |
Time Frame: | Day 28, Month 3, 6, 9, and 12 |
Safety Issue: | |
Description: | |
Measure: | Time To Progression by Lugano Criteria |
Time Frame: | Day 28, Month 3, 6, 9, and 12 |
Safety Issue: | |
Description: | |
Measure: | Overall Survival by Lugano Criteria |
Time Frame: | Day 28, Month 3, 6, 9, and 12 |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Adicet Bio, Inc |
Trial Keywords
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Immune System Diseases
- Cyclophosphamide
- Bendamustine
- Fludarabine
- Interleukin-2
- T cells,gamma delta
- Immunotherapy, Adoptive
- Antigens, CD20
Last Updated
August 27, 2021