54 Participants Needed

Ipilimumab + Decitabine for Acute Myeloid Leukemia

Recruiting at 10 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of ipilimumab when given together with decitabine in treating patients with myelodysplastic syndrome or acute myeloid leukemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ipilimumab and decitabine may work better in treating patients with relapsed or refractory myelodysplastic syndrome or acute myeloid leukemia.

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.

What data supports the effectiveness of the drug combination of Ipilimumab and Decitabine for Acute Myeloid Leukemia?

Research shows that Decitabine, when combined with other drugs, has been studied for its effectiveness in treating acute myeloid leukemia (AML), particularly in older patients or those with relapsed or refractory AML. However, there is no direct evidence from the provided studies about the specific combination of Ipilimumab and Decitabine for AML.12345

Is the combination of Ipilimumab and Decitabine safe for humans?

Ipilimumab, used for treating melanoma, can cause immune-related side effects like skin rashes, diarrhea, and inflammation of the colon. Most side effects are mild to moderate, but some can be severe. Decitabine, often used for blood cancers, has its own side effects, but specific safety data for the combination with Ipilimumab is not available.678910

What makes the drug combination of Ipilimumab and Decitabine unique for treating acute myeloid leukemia?

The combination of Ipilimumab and Decitabine for acute myeloid leukemia is unique because it pairs an immune checkpoint inhibitor (Ipilimumab) with a DNA methylation inhibitor (Decitabine), potentially enhancing the immune system's ability to fight cancer cells while also altering the cancer cell's DNA to make them more susceptible to treatment. This approach is different from standard chemotherapy, which primarily targets rapidly dividing cells.23111213

Research Team

JS

Jacqueline S Garcia

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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.
See 20 more

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.
See 12 more

Timeline

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

Treatment Details

Interventions

  • Decitabine
  • Ipilimumab
Trial OverviewThe 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.
Participant Groups
6Treatment groups
Experimental Treatment
Group I: Arm B (decitabine, ipilimumab), transplant naive, Dose Level 2Experimental Treatment2 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 1Experimental Treatment2 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 0Experimental Treatment2 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 2Experimental Treatment2 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 1Experimental Treatment2 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 0Experimental Treatment2 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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.
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]
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.
[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]
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.
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]

References

Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. [2019]
Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS. [2023]
[Clinical resarch of decitabine combined with modified CAG regimen for treatment of relapsed or refractory acute myeloid leukemia]. [2022]
[Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia]. [2023]
Successful Management of Decitabine prior to Full-Dose Idarubicin and Cytarabine in the Treatment of Refractory/Recurrent Acute Myeloid Leukemia. [2018]
CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. [2022]
Adjuvant Therapy of Melanoma. [2022]
Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis. [2020]
Ipilimumab-Based Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events With Ipilimumab Monotherapy and Combination Therapy With Nivolumab. [2018]
10.United Statespubmed.ncbi.nlm.nih.gov
Long-term Follow-up of Standard-Dose Pembrolizumab Plus Reduced-Dose Ipilimumab in Patients with Advanced Melanoma: KEYNOTE-029 Part 1B. [2021]
[The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms]. [2022]
Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target. [2021]
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. [2018]