Leukemia
Conditions
Keywords
Drug Therapy, AML, acute myeloid leukemia, cell therapy, allogenic, gamma delta T cells, relapsed/ refractory
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 and Japan. The overall time to participate in the study is approximately 14 months.
Interventions
DRUGGDX012
GDX012 suspension for IV infusion.
Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care.
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) to Determine the Maximum Tolerated Dose (MTD) of GDX012 | Up to 30 days post infusion | DLTs were defined as events occurring by Day 30 after the first GDX012 infusion considered related to GDX012 if they could not be explained by underlying disease, prior therapy, intercurrent illness, or lymphodepleting chemotherapy. Events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. DLTs included severe non-hematologic toxicities (Grade 3-4, unresolved or involving vital organs), Grade ≥3 graft versus host disease (GvHD) graded per the Mount Sinai Acute GvHD International Consortium recommendations and 2014 National Institutes of Health (NIH) Consensus, Grade 3-4 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) criteria, Grade ≥3 infusion reactions or tumor lysis syndrome (TLS), persistent cytopenia or marrow hypocellularity, and any Grade 5 toxicity attributable to GDX012. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Up to 14 months | An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event or a previous condition that has increased in severity or frequency since the administration of study drug. TEAEs are defined as any AE that begins on or after the initiation of treatment with a study intervention or any existing event that worsens following exposure to the study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Disease Response | Up to 14 months | Percentage of participants with disease response included participants who achieved complete response (CR), complete response with partial hematologic recovery (CRh), or complete response with incomplete hematologic recovery (CRi), based on responses assessed by the investigator according to the 2022 European Leukemia Net \[ELN\] response criteria for acute myeloid leukemia (AML). CR was defined as the sum of complete remission and complete remission without measurable residual disease (MRD). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. |
| Percentage of Participants With Measurable Residual Disease (MRD) Negative Status as Determined by Flow Cytometry | Up to 14 months | The MRD negative status was defined as (less than) \<0.1% detectable disease based on local assessment of bone marrow and/or blood. |
| Duration of Response (DOR) | Up to 14 months | DOR was planned to be assessed for participants with CR, CRh, or CRi and was defined as the time from the date of first documented CR, CRh, or CRi to the date of first documented relapse or death from any cause, whichever comes first. CR was defined as the sum of Complete Remission and Complete Remission without MRD. CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD- . |
| Event-free Survival (EFS) | Up to 14 months | EFS was defined as the time from the date of the first GDX012 administration to the date of treatment failure, relapse for those who achieved CR, CRh, or CRi, or death from any cause, whichever came first. CR was defined as the sum of Complete Remission and Complete Remission without MRD (CRMRD-). CRh was defined as the sum of CRh and CRhMRD-. CRi was defined as the sum of CRi and CRiMRD-. EFS was analyzed using the Kaplan-Meier method. |
| Overall Survival (OS) | Up to 14 months | OS was defined as the time from the date of the first GDX012 administration to the date of death from any cause. Participants without documentation of death at the time of analysis were censored at the last contact date. OS was analyzed using the Kaplan-Meier method. |
Countries
Japan, United States
Contacts
STUDY_DIRECTORMedical Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at 10 investigative sites in United States and Japan from 11 July 2023 to 30 November 2025.
Pre-assignment details
A total of 16 adult participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) were enrolled in the study and treated with GDX012. The Phase 2a of the study was not initiated as the study was terminated early due to the business decision.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 2 / 3 | 7 / 8 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 8 / 8 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 3 / 8 |
Outcome results
None listed