GDX012 for Acute Myeloid Leukemia

Not currently recruiting at 17 trial locations

Overseen By Takeda Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Takeda

Disqualifiers: Acute promyelocytic leukemia, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called GDX012 (Allogeneic Variable Delta 1 Gamma-Delta T-Cell Therapy) for certain cancers, with a focus on Acute Myeloid Leukemia (AML). The study aims to determine the treatment's safety, patient tolerance, and optimal dosage. People with AML that has returned or isn't responding to treatment might be suitable candidates, especially if they can't receive a stem cell transplant. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GDX012, a cell therapy being tested for Acute Myeloid Leukemia (AML), uses a type of immune cell called gamma delta T cells, which may help control AML. Early studies are examining the effectiveness and safety of these cells.

Although large-scale safety data is not yet available, researchers are exploring this treatment because it might be well-tolerated. Treatments at this testing stage have shown some safety promise in earlier tests. Ongoing research will provide more detailed safety information in the future.

Prospective trial participants should know that researchers are closely monitoring both the benefits and any possible side effects of GDX012. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia (AML), which often include chemotherapy and stem cell transplants, GDX012 offers a novel approach by using a weight-based intravenous infusion designed to target cancer cells more precisely after lymphodepleting chemotherapy. Researchers are excited about GDX012 because it introduces a new mechanism of action that might improve outcomes by directly engaging with specific cancer pathways. Additionally, the potential for a second dose in some patients could enhance its effectiveness, setting it apart from current one-time treatments.

What evidence suggests that GDX012 might be an effective treatment for Acute Myeloid Leukemia?

Research has shown that GDX012, a new cell therapy under investigation in this trial, may help treat Acute Myeloid Leukemia (AML). Studies have found that gamma delta T cells, a component of GDX012, can extend patient survival and reduce the risk of leukemia recurrence. In earlier trials, administering these cells to AML patients proved safe and positively impacted the disease. Specifically, some patients experienced longer periods without leukemia. This suggests that GDX012 could be a promising treatment option for AML. Participants in this trial will receive GDX012 following lymphodepleting chemotherapy, with different dose levels being tested. ^{1 2 4 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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

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.

I weigh at least 40 kg.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Chemotherapy Agents
• GDX012

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.

How Is the Trial Designed?

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.

GDX012 is already approved in United States for the following indications:

Approved in United States as GDX012 for:

• Acute Myeloid Leukemia (AML) - Orphan Drug Designation

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

Published Research Related to This Trial

In a study involving seven donor/recipient pairs, donor-derived Vdelta1(+) gammadelta(+) T cells were found to be activated and able to kill recipient acute lymphoblastic leukemia (ALL) cells, suggesting a potential therapeutic role in preventing relapse after bone marrow transplantation.

These gammadelta(+) T cells showed limited proliferation against unrelated HLA-mismatched cells, indicating that they could provide an effective treatment for refractory ALL without causing graft-versus-host disease, a common complication in transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human gammadelta(+) T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response. Lamb, LS., Musk, P., Ye, Z., et al.[2020]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05001451

Study of GDX012 in Patients With MRD Positive AML Individual Patients: Allows a single patient, with a serious disease or condition who cannot participate in a clinical trial, access to a drug or biological ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10900322/

Gamma delta T cells in acute myeloid leukemia Insights from murine models and clinical data in humans show improved overall survival, leukemia-free survival, reduced risk of relapse, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10139146/

A Phase I Trial of Allogeneic γδ T Lymphocytes From ... γδ T cell infusion in 7 patients was safe and feasible up to a cell dose of 108/kg and with preliminary evidence of disease activity in acute myeloid leukemia.

4. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT525/701631/Abstract-CT525-GDX012U-001-A-phase-1-open-label

Abstract CT525: GDX012U-001 A phase 1, open-label, dose ... GammaDelta Therapeutics has developed GDX012, a novel allogeneic cell therapy that is enriched for Vδ1+ γδ T cells for the treatment of AML.

5. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4846/500775/Phase-I-Trial-of-Allogeneic-Donor-Gamma-Delta-T

Phase I Trial of Allogeneic Donor Gamma Delta T Cell Infusion ... An ongoing phase 1/1b study is evaluating the safety and potential efficacy of ex vivo expanded donor GDT after reduced-intensity conditioning (RIC) allo-HCT.

6. cancerresearchhorizons.com cancerresearchhorizons.com/news-and-events/our-news/gammadelta-therapeutics-initiates-first-human-phase-1-trial-gdx012

GammaDelta Therapeutics initiates first-in-human phase 1 ... It has initiated a first-in-human Phase I clinical trial evaluating GDX012 for the treatment of acute myeloid leukaemia (AML).

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4826/533293/Phase-I-Trial-of-Ex-Vivo-Expanded-Donor-Gamma

Phase I Trial of Ex Vivo Expanded Donor Gamma Delta T Cell ... Phase I trial of ex vivo expanded Donor Gamma Delta T cell immunotherapy to prevent acute myeloid leukemia relapse after allogeneic transplantation.