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

Adicet Therapeutics

Status and phase: Terminated; Phase 1

Conditions: Lymphoma, Mantle-Cell; Lymphoma, Follicular; Marginal Zone Lymphoma; Lymphoma, Non-Hodgkin; Diffuse Large B Cell Lymphoma; Primary Mediastinal B-cell Lymphoma

Treatments: Genetic: ADI-001; Drug: Fludarabine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04735471

ADI-20200101

Details and patient eligibility

About

This is a Phase 1 dose escalation 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.

Full 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.

Enrollment: 34 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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34 participants in 3 patient groups

ADI-001 Dose Escalation

Experimental group

Description:

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).

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Genetic: ADI-001

ADI-001 Dose Extension

Experimental group

Description:

ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Genetic: ADI-001

ADI-001 Dose Expansion

Experimental group

Description:

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Genetic: ADI-001