Back to resultsA Safety and Efficacy Study of ADI-001, an Anti-CD20 Allogeneic Gamma Delta CAR-T, in Subjects With B Cell Malignancies (GLEAN-1)
Primary Purpose
Lymphoma, Follicular, Lymphoma, Mantle-Cell, Marginal Zone Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ADI-001
Fludarabine
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Follicular focused on measuring B-cell lymphoma, CAR-T, Cell Therapy, Allogeneic Cell Therapy, T cells, gamma delta, Immunotherapy, Adoptive, Antigens, CD20
Eligibility Criteria
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:
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])
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
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)
Sites / Locations
- Stanford University Medical CenterRecruiting
- University of Miami- Sylvester Comprehensive Cancer CenterRecruiting
- Northside Hospital Blood and Marrow Transplant Group of GeorgiaRecruiting
- The State University of IowaRecruiting
- Norton Cancer InstituteRecruiting
- Baylor Scott & White Research InstituteRecruiting
- MD Anderson Cancer CenterRecruiting
- Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
ADI-001 Dose Escalation
ADI-001 Dose Extension
ADI-001 Dose Expansion
Arm 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).
ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
Outcomes
Primary Outcome Measures
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).
Proportion of treatment emergent and treatment related adverse events
This primary endpoint will be used to determine the MTD/MAD of ADI-001
Secondary Outcome Measures
Frequency and persistence of ADI-001
Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood
Overall Response Rate by Lugano Criteria
Duration of Response
Progression Free Survival
Time To Progression
Overall Survival
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04735471
Brief Title
A Safety and Efficacy Study of ADI-001, an Anti-CD20 Allogeneic Gamma Delta CAR-T, in Subjects With B Cell Malignancies
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 4, 2021 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adicet Bio, Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a Phase 1 dose esclation 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.
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Follicular, Lymphoma, Mantle-Cell, Marginal Zone Lymphoma, Primary Mediastinal B-cell Lymphoma, Diffuse Large B Cell Lymphoma, Lymphoma, Non-Hodgkin
Keywords
B-cell lymphoma, CAR-T, Cell Therapy, Allogeneic Cell Therapy, T cells, gamma delta, Immunotherapy, Adoptive, Antigens, CD20
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
3+3 Dose Escalation Design
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
78 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ADI-001 Dose Escalation
Arm Type
Experimental
Arm 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).
Arm Title
ADI-001 Dose Extension
Arm Type
Experimental
Arm Description
ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).
Arm Title
ADI-001 Dose Expansion
Arm Type
Experimental
Arm Description
Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).
Intervention Type
Genetic
Intervention Name(s)
ADI-001
Intervention Description
Anti-CD20 CAR-T
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Chemotherapy for Lymphodepletion
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Chemotherapy for Lymphodepletion
Primary Outcome Measure Information:
Title
The Incidence of Subjects with Dose Limiting Toxicities within each dose level cohort
Description
This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).
Time Frame
Day 28
Title
Proportion of treatment emergent and treatment related adverse events
Description
This primary endpoint will be used to determine the MTD/MAD of ADI-001
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Frequency and persistence of ADI-001
Description
Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood
Time Frame
Day 1 through Month 12
Title
Overall Response Rate by Lugano Criteria
Time Frame
Day 28, Month 3, 6, 9, and 12
Title
Duration of Response
Time Frame
Day 28, Month 3, 6, 9, and 12
Title
Progression Free Survival
Time Frame
Day 28, Month 3, 6, 9, and 12
Title
Time To Progression
Time Frame
Day 28, Month 3, 6, 9, and 12
Title
Overall Survival
Time Frame
Day 28, Month 3, 6, 9, and 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
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])
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
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rose Lai, MD
Phone
6263181179
Email
clinicaltrials@adicetbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rose Lai, MD
Organizational Affiliation
Adicet Bio
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Miklos, MD
Phone
650-723-0822
Email
dmiklos@stanford.edu
Facility Name
University of Miami- Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jay Spiegel, MD
Email
spiegelj@med.miami.edu
Facility Name
Northside Hospital Blood and Marrow Transplant Group of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asad Bashey, MD
Email
abashey@btmga.com
Facility Name
The State University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Umar Farooq, MD
Email
umar-farooq@uiowa.edu
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Don A Stevens, MD
Phone
502-899-3366
Email
Don.Stevens@nortonhealthcare.org
Facility Name
Baylor Scott & White Research Institute
City
Dallas
State/Province
Texas
ZIP/Postal Code
75204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Houston Holmes, MD
Phone
214-370-1000
Email
houston.holmes@usoncology.com
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sattva Neelapu, MD
Email
SNeelapu@mdanderson.org
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mehdi Hamadani, MD
Phone
414-805-0505
Email
mhamadani@mcw.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35136603
Citation
Nishimoto KP, Barca T, Azameera A, Makkouk A, Romero JM, Bai L, Brodey MM, Kennedy-Wilde J, Shao H, Papaioannou S, Doan A, Masri C, Hoang NT, Tessman H, Ramanathan VD, Giner-Rubio A, Delfino F, Sharma K, Bray K, Hoopes M, Satpayev D, Sengupta R, Herrman M, Abbot SE, Aftab BT, An Z, Panuganti S, Hayes SM. Allogeneic CD20-targeted gammadelta T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models. Clin Transl Immunology. 2022 Feb 2;11(2):e1373. doi: 10.1002/cti2.1373. eCollection 2022.
Results Reference
derived
Learn more about this trial
A Safety and Efficacy Study of ADI-001, an Anti-CD20 Allogeneic Gamma Delta CAR-T, in Subjects With B Cell Malignancies
We'll reach out to this number within 24 hrs