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Trials / Recruiting

RecruitingNCT03969446

Pembrolizumab and Decitabine With or Without Venetoclax in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome That Is Newly-Diagnosed, Recurrent, or Refractory

Phase 1b Study of Pembrolizumab, Decitabine +/- Venetoclax Combination Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
54 (estimated)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase Ib trial studies the side effects and best dose of pembrolizumab and how well it works in combination with decitabine with or without venetoclax in treating patients with acute myeloid leukemia or myelodysplastic syndrome that is newly-diagnosed, has come back (recurrent), or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. This trial may help doctors find the best dose of pembrolizumab that can be safely given in combination with decitabine with or without venetoclax, and to determine what side effects are seen with this treatment.

Detailed description

PRIMARY OBJECTIVES: I. Assess the safety and tolerability of pembrolizumab combined with decitabine, with or without the addition of venetoclax (treatment cohorts 1 and 2), by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (ACUTE MYELOID LEUKEMIA \[AML\] ARM) II. Assess the safety and tolerability of pembrolizumab combined with decitabine, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration. (MYELODYSPLASTIC SYNDROME \[MDS\] ARM) III. Determine the maximum tolerated dose(s)/schedule (MTD) and recommended phase 2 dose(s)/ schedule (RP2D) within each treatment arm/cohort. III. Obtain preliminary estimates of complete remission (CR/CR with incomplete hematologic recovery \[CRi\]) rate(s) within each treatment arm/cohort. SECONDARY OBJECTIVES: I. Obtain estimates of remission duration and survival probabilities (overall and progression-free) at 2 years. II. Explore the possible association between pre-treatment PD-1, PD-L1, and PD-L2 and clinical response. III. Evaluate change in PD-1, PD-L1, PD-L2 levels as a result of the combination therapy. IV. Explore the possible association between specific T cell subsets (e.g. CD4 T regulatory cells, T naive, effector and memory cells), other immunological correlatives (e.g. T-cell receptor \[TCR\] repertoire analysis) including post-treatment changes, and clinical response to combination therapy. OUTLINE: Patients are assigned to 1 of 2 arms. ARM I: Patients with AML are assigned to 1 of 2 cohorts. COHORT I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10. Patients who achieve a CR receive decitabine on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity. COHORT II: Patients with pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine IV over 1 hour on days 1-10 or 1-5. Patients who achieve a CR receive decitabine on days 1-5. Patients also receive venetoclax orally (PO) once daily (QD) on days 1-14. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity. ARM II: Patients with MDS receive pembrolizumab IV over 30 minutes on days 1 and 22 and decitabine over 1 hour on days 1-5. Treatment repeats every 42 days for up to 8 cycles or 1 year from start of therapy, whichever comes first, in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients who have discontinued therapy and have not progressed are followed up at 6, 12, and 24 months post-start of treatment. Patients who progress during treatment are followed up every 3 months for 2 years.

Conditions

Interventions

TypeNameDescription
DRUGDecitabineGiven IV
BIOLOGICALPembrolizumabGiven IV
DRUGVenetoclaxGiven PO

Timeline

Start date
2020-05-04
Primary completion
2027-07-04
Completion
2027-07-04
First posted
2019-05-31
Last updated
2026-03-05

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT03969446. Inclusion in this directory is not an endorsement.