A Study of GDX012 in Adults With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
=================
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: GDX012 Dose 1 GDX012 Dose 2 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.

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

Conditions
-----------------
Leukemia

Intervention / Treatment
-----------------
* Drug: GDX012
* Drug: Chemotherapy Agents


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Total body weight of ≥40 kg. Must have pathologically confirmed relapsed or refractory acute myeloid leukemia (R/R AML) including: 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. 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. During dose escalation, participants must be ineligible for hematopoietic stem cell transplantation (HSCT). Must have an anticipated life expectancy of >3 months before lymphodepletion. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Participants must have adequate renal, cardiac, hepatic, pulmonary and bone marrow function as defined by the protocol. Exclusion criteria: Diagnosis of acute promyelocytic leukemia. Has received or plans to receive any of the excluded therapy/treatment within the specified timeframe before lymphodepleting chemotherapy as defined by the protocol. Prior allogeneic HSCT within 3 months of signing informed consent form (ICF) or with ongoing requirement for systemic graft-versus-host therapy. Active central nervous system (CNS) involvement. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose Escalation of GDX012<br>Participants will receive GDX012 weight-based dose as intravenous (IV) infusion on Day 1 of Phase 1 after lymphodepleting chemotherapy. Three dose levels of GDX012 will be tested in Phase 1. Some participants may be eligible for a second dose. | Drug: GDX012<br>* GDX012 suspension for IV infusion.<br>Drug: Chemotherapy Agents<br>* Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care.<br>|
| Experimental: Phase 2a: GDX012<br>Participants will receive GDX012 (weight-based) IV infusion at pre-selected one or two dose levels from Phase 1, on Day 1 after lymphodepleting chemotherapy. Some participants may be eligible for a second dose. | Drug: GDX012<br>* GDX012 suspension for IV infusion.<br>Drug: Chemotherapy Agents<br>* Chemotherapy agents (fludarabine/cyclophosphamide) as per standard of care.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLTs) |  | Up to 1 month | 
| Maximum Tolerated Dose (MTD) of GDX012 |  | Up to 1 month | 
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. | Up to 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease Response | Disease response includes participants achieving complete response [CR] complete response with incomplete hematologic recovery [CRi] (complete response with partial hematologic recovery [CRh] morphological leukemia-free state [MLFS] or partial response [PR] (based on 2022 European Leukemia Net [ELN] response criteria for AML after GDX012 administration. | Up to 14 months | 
| Number of Participants With Measurable Residual Disease (MRD) Negative Status as Determined by Flow Cytometry |  | Up to 14 months | 
| Duration of Response (DOR) | DOR is defined as the time from the date of first documented CR, CRh, or CRi to the date of relapse or death. | Up to 14 months | 
| Event-free Survival (EFS) | EFS is defined as the time from the date of the first GDX012 administration to the date of treatment failure, relapse or death, whichever comes first. | Up to 14 months | 
| Overall Survival (OS) | OS is defined as the time from the date of the first GDX012 administration to the date of death. | Up to 14 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug Therapy, AML, acute myeloid leukemia, cell therapy, allogenic, gamma delta T cells, relapsed/ refractory