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

Lymphoma, Non-Hodgkin Clinical Trial

— GLEAN-1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04735471
• Other study ID #: ADI-20200101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2021
• Est. completion date: December 31, 2027

Study information

• Verified date: April 2024
• Source: Adicet Bio, Inc
• Contact: Adicet Medical Director
• Phone: 650-503-9095
• Email: clinicaltrials[@]adicetbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Genetic:
• ADI-001
Anti-CD20 CAR-T

Drug:
• Fludarabine
Chemotherapy for Lymphodepletion
• Cyclophosphamide
Chemotherapy for Lymphodepletion

Locations

Country	Name	City	State
United States	Northside Hospital Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Baylor Scott & White Research Institute	Dallas	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	The State University of Iowa	Iowa City	Iowa
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Miami- Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Swedish Cancer Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Adicet Bio, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort	This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).	Day 28
Primary	Proportion of treatment emergent and treatment related adverse events	This primary endpoint will be used to determine the MTD/MAD of ADI-001	1 year
Secondary	Frequency and persistence of ADI-001	Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood	Day 1 through Month 12
Secondary	Overall Response Rate by Lugano Criteria		Day 28, Month 3, 6, 9, and 12
Secondary	Duration of Response		Day 28, Month 3, 6, 9, and 12
Secondary	Progression Free Survival		Day 28, Month 3, 6, 9, and 12
Secondary	Time To Progression		Day 28, Month 3, 6, 9, and 12
Secondary	Overall Survival		Day 28, Month 3, 6, 9, and 12