Clinical trial NCT05886491: A Study of GDX012 in Adults With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Phase 1/2a, Open-Label, Dose Escalation, and Dose Expansion Study to Assess the Safety and Efficacy of GDX012 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: Drug Therapy
AML
acute myeloid leukemia
cell therapy
allogenic
gamma delta T cells
relapsed/ refractory
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-06-02
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: GDX012 is a novel cell therapy developed for the treatment of certain types of cancer, including Acute Myeloid Leukemia (AML). The main aims of the study are to learn how safe GDX012 is, how treatment with GDX012 is tolerated and to determine the best dose of GDX012.

Detailed description: The drug being tested in this study is called GDX012. GDX012 is being tested to evaluate the safety and tolerability in adult participants with AML.

The study will enroll approximately 53 patients in two phases, dose escalation and dose expansion.

During Phase 1 (sequential dose escalation), participants will be assigned to one of the following treatment groups each consisting of 3 to 6 participants to receive GDX012 at one of the three dose levels:

1. GDX012 Dose 1
2. GDX012 Dose 2
3. GDX012 Dose 3

Upon completion of Phase 1, 1 to 2 dose levels will be selected for Phase 2a of the study. At the completion of Phase 2a of the study a single dose may be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D) for future study.

This multi-center trial will be conducted in the United States. The overall time to participate in the study is approximately 14 months.

Eligibility criteria: Inclusion criteria:

1. Total body weight of ≥40 kg.
2. Must have pathologically confirmed relapsed or refractory acute myeloid leukemia (R/R AML) including:

   1. Relapsed AML is defined as ≥5% blasts in the bone marrow (BM) or peripheral blood at any time after achieving a CR, CRh, Cri, or MLFS.
   2. Refractory AML is defined as failure to achieve a CR, CRh, Cri, or MLFS after 1 of the following regimens:

   i. Two courses of intensive induction chemotherapy. ii. At least 2 cycles of hypomethylating agent (HMA) or low-dose, cytarabine-based combination regimen.

   iii. At least 4 cycles of HMA monotherapy.
3. During dose escalation, participants must be ineligible for hematopoietic stem cell transplantation (HSCT).
4. Must have an anticipated life expectancy of \>3 months before lymphodepletion.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
6. Participants must have adequate renal, cardiac, hepatic, pulmonary and bone marrow function as defined by the protocol.

Exclusion criteria:

1. Diagnosis of acute promyelocytic leukemia.
2. Has received or plans to receive any of the excluded therapy/treatment within the specified timeframe before lymphodepleting chemotherapy as defined by the protocol.
3. Prior allogeneic HSCT within 3 months of signing informed consent form (ICF) or with ongoing requirement for systemic graft-versus-host therapy.
4. Active central nervous system (CNS) involvement.
5. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg. cervix, bladder, breast) low grade prostate cancer without treatment requirement unless in remission without treatment for ≥2 years.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Up to 1 month
measure: Maximum Tolerated Dose (MTD) of GDX012
timeFrame: Up to 1 month
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 14 months
Secondary outcomes:
measure: Number of Participants With Disease Response
timeFrame: Up to 14 months
measure: Number of Participants With Measurable Residual Disease (MRD) Negative Status as Determined by Flow Cytometry
timeFrame: Up to 14 months
measure: Duration of Response (DOR)
timeFrame: Up to 14 months
measure: Event-free Survival (EFS)
timeFrame: Up to 14 months
measure: Overall Survival (OS)
timeFrame: Up to 14 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) Hospital
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Sarah Cannon/CBCI
state: Colorado
city: Chicago
country: United States
facility: Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Thomas Jefferson University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Nashville
country: United States
facility: Tri-Star BMT/Sarah Cannon Nashville
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: