GDX012 for Acute Myeloid Leukemia

Recruiting at16 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Takeda

Disqualifiers: Acute promyelocytic leukemia, CNS involvement, others

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing GDX012, a new cell therapy, in adult patients with Acute Myeloid Leukemia (AML). The goal is to see how safe and tolerable the treatment is and to find the best dose. GDX012 works by using specially modified cells to attack cancer cells.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain therapies or treatments are excluded within a specific timeframe before starting the trial, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment GDX012 for Acute Myeloid Leukemia?

Research shows that gamma delta (γδ) T cells, a key component of GDX012, can effectively kill leukemia cells in the lab and in animal models. These cells have unique properties that make them promising for cancer treatment, including their ability to target cancer cells without needing specific markers, which enhances their potential as a therapy for blood cancers like acute myeloid leukemia. ^{1 2 3 4 5}

Is GDX012 safe for humans?

The research on gamma-delta T cells, which are part of the GDX012 treatment, shows they have been used in humans and have the ability to target and kill leukemia cells. However, specific safety data for GDX012 in humans is not detailed in the available studies. ^{1 2 3 4 6}

How is the treatment GDX012 unique for acute myeloid leukemia?

GDX012 is unique because it uses a type of immune cell called gamma-delta T cells, which can recognize and kill cancer cells without needing to match the patient's tissue type. This makes it a promising option for treating acute myeloid leukemia, as it can target and destroy leukemia cells effectively. ^{1 2 3 4 7}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

Adults with a body weight of at least 40 kg who have relapsed or refractory Acute Myeloid Leukemia (AML) and are not eligible for stem cell transplantation can join. They should be in relatively good health otherwise, with an expected lifespan over 3 months and able to perform daily activities with little or no assistance.

Inclusion Criteria

I weigh at least 40 kg.

Must have pathologically confirmed relapsed or refractory acute myeloid leukemia (R/R AML) including: Relapsed AML defined as ≥5% blasts in the bone marrow (BM) or peripheral blood after achieving a CR, CRh, Cri, or MLFS. Refractory AML 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

I have been diagnosed with acute promyelocytic leukemia.

I have not received, nor plan to receive, any excluded treatments before my specific chemotherapy.

I had a bone marrow transplant less than 3 months ago or still need treatment for graft-versus-host disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Participants receive GDX012 at one of three dose levels after lymphodepleting chemotherapy. Some may receive a second dose.

Up to 14 months

Multiple visits for dose administration and monitoring

Phase 2a: Dose Expansion

Participants receive GDX012 at pre-selected dose levels from Phase 1 after lymphodepleting chemotherapy. Some may receive a second dose.

Up to 14 months

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Chemotherapy Agents (Chemotherapy Agent)
• GDX012 (CAR T-cell Therapy)

Trial Overview The trial is testing GDX012, a new cell therapy for AML. It aims to find out how safe the treatment is, how well patients tolerate it, and determine the best dose when combined with chemotherapy agents.

Participant Groups

Group I: Phase 2a: GDX012 Experimental Treatment 2 Interventions

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.

Group II: Phase 1: Dose Escalation of GDX012 Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

γδ T cells can be effectively stimulated to target and kill leukemic blasts, showing promise for immunotherapy in acute myeloid leukemia (AML).

Developing immunotherapeutic strategies that utilize γδ T cells could potentially provide a treatment option applicable to all AML patients, addressing a significant challenge in current research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of acute myeloid leukemia based on γδ T cells. Gertner-Dardenne, J., Fauriat, C., Vey, N., et al.[2021]

In a study of 33 acute myeloid leukemia (AML) patients, gammadelta T cell levels were found to be lower compared to healthy individuals, particularly in patients with high blast counts before treatment, suggesting a potential link between gammadelta T cell frequency and disease severity.

The study demonstrated that gammadelta T cells from AML patients can effectively kill leukemic cells in vitro and showed significant increases in patients experiencing early relapse, indicating their potential as therapeutic agents in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flow cytometric assessment of autologous gammadelta T cells in patients with acute myeloid leukemia: potential effector cells for immunotherapy? Aswald, JM., Wang, XH., Aswald, S., et al.[2020]

A new protocol was developed to effectively expand γδ T cells from healthy donors for use in treating patients with acute myeloid leukemia (AML), achieving over 229,000-fold expansion of these cells.

The expansion process involves activating γδ T cells with FDA-approved zoledronic acid and interleukin-2, followed by purification and further expansion using engineered artificial antigen-presenting cells, making it a promising approach for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion and Enrichment of Gamma-Delta (γδ) T Cells from Apheresed Human Product. Landin, AM., Cox, C., Yu, B., et al.[2021]

Vγ9Vδ2 T cells in acute myeloid leukemia (AML) patients showed normal numbers but an unusual differentiation pattern, which normalized after chemotherapy, indicating that leukemic cells may disrupt T cell development.

These T cells can effectively kill AML cells through specific pathways and have shown potential for enhancing survival in a mouse model, suggesting they could be a promising therapeutic option for AML when optimally activated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Vγ9Vδ2 T cells specifically recognize and kill acute myeloid leukemic blasts. Gertner-Dardenne, J., Castellano, R., Mamessier, E., et al.[2020]

Gamma delta (γδ) T cells are a promising option for cancer immunotherapy, particularly for hematologic malignancies, due to their unique properties that allow them to target tumors without major histocompatibility complex (MHC) restrictions.

Their ability to act like antigen-presenting cells and their ease of expansion from peripheral blood make γδ T cells a strong candidate for allogeneic adoptive cellular therapy, potentially improving treatment outcomes for patients with difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic gamma delta T cells as adoptive cellular therapy for hematologic malignancies. Jhita, N., Raikar, SS.[2022]

Human gamma delta T cells (GDTc) can be effectively expanded in vitro to create highly cytotoxic cells that target and kill leukemia cells, showing promise for cellular immunotherapy.

In a mouse model, treatment with these expanded GDTc significantly reduced leukemia burden in the bone marrow, indicating their potential effectiveness in treating hematological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-leukemia activity of in vitro-expanded human gamma delta T cells in a xenogeneic Ph+ leukemia model. Siegers, GM., Felizardo, TC., Mathieson, AM., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy of acute myeloid leukemia based on γδ T cells. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Flow cytometric assessment of autologous gammadelta T cells in patients with acute myeloid leukemia: potential effector cells for immunotherapy? [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Expansion and Enrichment of Gamma-Delta (γδ) T Cells from Apheresed Human Product. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Human Vγ9Vδ2 T cells specifically recognize and kill acute myeloid leukemic blasts. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Allogeneic gamma delta T cells as adoptive cellular therapy for hematologic malignancies. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Anti-leukemia activity of in vitro-expanded human gamma delta T cells in a xenogeneic Ph+ leukemia model. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response. [2020]