Ipilimumab + Decitabine for Acute Myeloid Leukemia

Not currently recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anti-CTLA-4, Anti-PD 1

Disqualifiers: CNS leukemia, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with myelodysplastic syndrome or acute myeloid leukemia, particularly if the disease has returned after treatment or has not responded. The focus is on combining two drugs: ipilimumab, an immunotherapy that helps the immune system attack cancer, and decitabine, a chemotherapy drug that stops cancer cells from growing. Patients who have experienced a return or resistance of these specific blood-related cancers, or who are new to treatment and have severe forms of the disease, might be suitable candidates. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications more than 2 weeks before starting treatment. If you are on systemic corticosteroids, you must reduce the dose to 5 mg/day or less of prednisone (or equivalent) for more than 1 week before starting treatment. Topical steroids are allowed.

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

Research explores the safety and effectiveness of combining two drugs, ipilimumab and decitabine, for patients with certain blood cancers. In a study with 54 patients, over half (52%) benefited from this treatment.

Ipilimumab, an immunotherapy, helps the immune system attack cancer cells. Decitabine, a chemotherapy drug, stops cancer cells from growing and spreading. Together, these drugs aim to be more effective against recurrent or hard-to-treat cancers.

Regarding safety, this treatment remains in early testing stages. Researchers are determining the best dose and closely monitoring patient responses. Although more information is needed to fully understand its safety, initial results suggest some patients tolerate it well, with researchers focusing on any side effects.

These studies are crucial to ensure the treatment is as safe as possible while offering potential benefits for patients with difficult-to-treat cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ipilimumab and Decitabine for treating Acute Myeloid Leukemia (AML) because it targets the immune system in a novel way. Most current treatments for AML, like chemotherapy, focus on directly killing cancer cells. However, Ipilimumab is an immunotherapy drug that boosts the immune system's ability to fight cancer by targeting CTLA-4, a protein that normally helps keep immune responses in check. This approach, combined with Decitabine's role in reactivating genes that suppress tumor growth, offers a dual-action strategy. This has the potential to improve outcomes for patients who have undergone allogeneic stem cell transplantation or have not received a transplant, providing hope for better management of AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research shows that combining ipilimumab and decitabine may help treat patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this trial, participants will receive different dose levels of this combination, either post allo-HCT or as transplant-naive patients. Previous studies demonstrated that this combination improved the condition of over half of the patients, with a response rate of 52%. Ipilimumab boosts the immune system to fight cancer cells, while decitabine is a chemotherapy drug that prevents cancer cells from growing and spreading. Together, they aim to be more effective in treating these challenging conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Jacqueline S Garcia

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eligible participants may have had certain treatments like chemotherapy, stem cell transplant, and must be in a stable condition. They should not have severe autoimmune diseases, active infections that aren't controlled, other cancers within the last 2 years, or known brain involvement by leukemia.

Inclusion Criteria

I am 75 or older with newly diagnosed or secondary AML and have not received treatment.

My MDS has returned after some improvement.

I haven't taken strong immune system medications for more than 2 weeks, or have been on a low dose of steroids for over a week.

Exclusion Criteria

I haven't had any other cancers for at least 2 years.

I received donor lymphocyte infusion within the last 8 weeks after a transplant.

You cannot participate if you are currently taking any other experimental medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming

Patients receive decitabine intravenously over 60 minutes on days 1-5 out of 28 days

4 weeks

5 visits (in-person)

Induction

Patients receive decitabine and ipilimumab intravenously, treatment repeats every 28 days for up to 4 cycles

16 weeks

5 visits per cycle (in-person)

Maintenance

Patients receive decitabine and ipilimumab intravenously, treatment repeats every 4 or 8 weeks for up to 4 cycles

16-32 weeks

5 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Ipilimumab

Trial Overview The trial tests the combination of Ipilimumab (an immunotherapy drug) and Decitabine (a chemotherapy drug) to see if they're more effective together against MDS/AML that's come back or hasn't responded to treatment. It aims to find the safest dose with the least side effects.

How Is the Trial Designed?

Group I: Arm B (decitabine, ipilimumab), transplant naive, Dose Level 2 Experimental Treatment 2 Interventions

PRIMING PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (10 mg/kg) over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (10 mg/kg) over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (decitabine, ipilimumab), transplant naive, Dose Level 1 Experimental Treatment 2 Interventions

PRIMING PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (5 mg/kg) over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (5 mg/kg) over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm B (decitabine, ipilimumab), transplant naive, Dose Level 0 Experimental Treatment 2 Interventions

PRIMING PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (3 mg/kg) over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Transplant naive patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (3 mg/kg) over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group IV: Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 2 Experimental Treatment 2 Interventions

PRIMING PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (10 mg/kg) over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (10 mg/kg) over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group V: Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 1 Experimental Treatment 2 Interventions

PRIMING PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (5 mg/kg) over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (5 mg/kg) over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group VI: Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 0 Experimental Treatment 2 Interventions

PRIMING PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days. INDUCTION PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (3 mg/kg) over 90 minutes on day 1. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Post allo-HCT patients receive decitabine IV over 60 minutes on days 1-5 and ipilimumab IV (3 mg/kg) over 90 minutes on day 1. Treatment repeats every 4 or 8 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

High-dose interleukin-2 (HDI) therapy for high-risk melanoma has shown significant improvements in relapse-free survival (RFS) in three trials and overall survival (OS) in two trials, indicating its efficacy as an adjuvant treatment.

Recent advancements have shifted the standard of care towards immune checkpoint inhibitors like nivolumab and pembrolizumab, as well as BRAF-MEK inhibitors (dabrafenib plus trametinib), which offer better RFS benefits and lower toxicity compared to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Therapy of Melanoma. Tarhini, AA.[2022]

The D-CAG regimen, which combines decitabine with a modified chemotherapy approach, achieved a complete remission (CR) rate of 69.4% in 59 elderly patients (≥70 years) with newly diagnosed acute myeloid leukemia (AML), indicating its efficacy in this age group.

The treatment was found to be safe, with major adverse reactions including grade 3-4 myelosuppression and infections, but it significantly improved overall survival (OS) and event-free survival (EFS) for patients who achieved CR, with median OS of 19.8 months compared to 6.4 months for those who did not respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia]. Cao, L., Jiang, ZQ., Liu, WJ., et al.[2023]

The combination of decitabine and idarubicin showed a synergistic effect in inducing cell death in various myeloid leukemia cell lines and primary AML cells, suggesting a more effective treatment strategy than decitabine alone.

This combination therapy not only inhibited tumor growth more effectively in mouse models but also triggered apoptosis and downregulated the Wnt/β-catenin pathway, which is linked to leukemia progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target. Li, K., Hu, C., Mei, C., et al.[2021]

Decitabine has been approved for treating older patients (65 years and older) with newly diagnosed acute myeloid leukemia (AML) who cannot undergo standard chemotherapy, showing a median overall survival of 7.7 months compared to 5.0 months for those receiving low-dose cytarabine or supportive care.

The treatment demonstrated improved response rates and progression-free survival, with a manageable safety profile, making it a valuable option for older patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Decitabine (Dacogen) for the Treatment of Adult Patients With Acute Myeloid Leukemia: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use. Nieto, M., Demolis, P., Béhanzin, E., et al.[2018]

In a study of 21 patients with refractory or recurrent acute myeloid leukemia (R/R AML), the triple therapy of decitabine, idarubicin, and cytarabine (D-IA) resulted in a 47.6% complete remission rate after one treatment cycle, indicating significant efficacy.

The treatment was generally well tolerated, with no treatment-related mortalities reported, although common side effects included hematological toxicity and infections, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia. Zhao, H., Xu, L., Yang, Y., et al.[2018]

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

The optimal biologic dose (OBD) of decitabine for treating acute myeloid leukemia (AML) was determined to be 20 mg/m²/day, which showed limited nonhematologic toxicity and promising clinical activity, with a response rate of 44% among 25 patients.

Combining decitabine with valproic acid (VA) resulted in dose-limiting encephalopathy at lower doses of VA, indicating safety concerns, while the clinical responses were similar whether patients received decitabine alone or in combination with VA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. Blum, W., Klisovic, RB., Hackanson, B., et al.[2019]

In a study of 84 patients with myeloid neoplasms, the combination of decitabine (DEC) and all-trans retinoic acid (ATRA) showed a significantly higher overall response rate (75%) compared to DEC alone (42.86%), indicating enhanced efficacy in treating these conditions.

The DEC/ATRA regimen demonstrated a similar efficacy to DEC combined with G-CSF priming, while also resulting in lower rates of severe bone marrow suppression and infections compared to the DEC/priming group, suggesting a safer profile for the DEC/ATRA combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms]. Wei, W., Liu, Y., Shang, LM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10122101/

Ipilimumab plus decitabine for patients with MDS or AML in ... In the first article, Garcia et al report on the results of a phase 1 trial of the combination in 54 patients, demonstrating overall response rate of 52% in ...

2. dana-farber.org dana-farber.org/clinical-trials/17-718

A Phase 1 Study of Ipilimumab in Combination with ... This phase I trial studies the side effects and best dose of ipilimumab when given together with decitabine in treating patients with myelodysplastic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01757639?tab=table

Ipilimumab in Treating Patients With Relapsed or ... This phase I trial studies the side effects and best dose of ipilimumab and how well it works in treating patients with high-risk myelodysplastic syndrome or ...

4. ega-archive.org ega-archive.org/studies/phs003292

Ipilimumab plus Decitabine for Patients with MDS or AML ... Design and Aims. This study was a phase 1 clinical trial investigating the combination of ipilimumab (IPI), a CTLA-4 checkpoint inhibitor, and decitabine ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs003015.v2.p1

dbGaP Study This study tested the combination of the CTLA-4 blocking antibody ipilimumab and the DNA methyltransferase inhibitor decitabine in advanced myeloid disease.

6. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT02890329

Ipilimumab and Decitabine in Treating Patients With ... Giving ipilimumab and decitabine may work better in treating patients with relapsed or refractory myelodysplastic syndrome or acute myeloid leukemia. Official ...

7. ash.confex.com ash.confex.com/ash/2020/webprogram/Paper136235.html

Paper: Safety and Efficacy of Decitabine Plus Ipilimumab in ... Adding decitabine (DAC) to IPI may increase efficacy of this approach in myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), and we ...