Clinical Trials /

A Study of ADI-001 in B Cell Malignancies

NCT04735471

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

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
FludarabineADI-001 Dose Escalation
CyclophosphamideADI-001 Dose Escalation
BendamustineADI-001 Dose Escalation
Interleukin-2ADI-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

NameTypeDescriptionInterventions
ADI-001 Dose EscalationExperimentalADI-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 ExpansionExperimentalADI-001 is administered via infusion to 3 NHL subtypes to confirm dose (Part 2).
  • Fludarabine
  • Cyclophosphamide
  • Bendamustine
ADI-001 in combination with Interleukin-2ExperimentalADI-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