Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT02890329 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 4 other identifiers: NCI-2016-0132617-71810026UM1CA186709
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Recurrent Acute Myeloid Leukemia; Previously Treated Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia; Recurrent Acute Myeloid Leukemia, Myelodysplasia-Related; Recurrent Myelodysplastic Syndrome; Refractory Acute Myeloid Leukemia; Refractory Myelodysplastic Syndrome; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (Recommended Phase 2 Dose) of Ipilimumab in Combination With Decitabine

  Defined as the highest dose at which 1 or fewer of 6 patients experience a dose limiting toxicity graded by Common Terminology Criteria for Adverse Events version 5.0 criteria.

  Monitoring for DLTs occurs continuously on treatment during the first 8 weeks of combination therapy (56 days from the start of combination) during the induction phase only.

Secondary Outcomes (5)

• Anti-leukemic Activity Described in Terms of Best Overall Response Rate

  Up to 52 weeks

• Anti-leukemic Activity Described in Terms of Progression Free Survival

  Time from registration to the earlier of progression or death due to any cause, assessed up to 52 weeks

• Anti-leukemic Activity Described in Terms of Overall Survival

  Time from registration to death due to any cause or censored at the date last known alive, assessed up to 52 weeks

• Incidence of Acute Graft-versus-host Disease

  Up to 100 days

• Incidence of Chronic Graft-versus-host Disease

  Up to 52 weeks

Other Outcomes (1)

• Ability of Absolute Lymphocyte Count to Predict Response

  Up to cycle 3 day 1

Study Arms (6)

Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 0

EXPERIMENTAL

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.

Drug: Decitabine; Biological: Ipilimumab

Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 1

EXPERIMENTAL

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.

Drug: Decitabine; Biological: Ipilimumab

Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 2

EXPERIMENTAL

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.

Drug: Decitabine; Biological: Ipilimumab

Arm B (decitabine, ipilimumab), transplant naive, Dose Level 0

EXPERIMENTAL

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.

Drug: Decitabine; Biological: Ipilimumab

Arm B (decitabine, ipilimumab), transplant naive, Dose Level 1

EXPERIMENTAL

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.

Drug: Decitabine; Biological: Ipilimumab

Arm B (decitabine, ipilimumab), transplant naive, Dose Level 2

EXPERIMENTAL

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.

Drug: Decitabine; Biological: Ipilimumab

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 0; Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 1; Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 2; Arm B (decitabine, ipilimumab), transplant naive, Dose Level 0; Arm B (decitabine, ipilimumab), transplant naive, Dose Level 1; Arm B (decitabine, ipilimumab), transplant naive, Dose Level 2

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 0; Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 1; Arm A (decitabine, ipilimumab), post allo-HCT, Dose Level 2; Arm B (decitabine, ipilimumab), transplant naive, Dose Level 0; Arm B (decitabine, ipilimumab), transplant naive, Dose Level 1; Arm B (decitabine, ipilimumab), transplant naive, Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with evidence of AML or myelodysplastic syndrome (MDS) that meet at least one of the following criteria:
• Relapsed AML: evidence of \>= 5% blasts in the bone marrow; or reappearance of blasts in the peripheral blood; or development of extramedullary disease (according to 2003 IWG criteria) who relapse after:
• Allogeneic hematopoietic stem cell transplant, or
• After one cycle of standard cytotoxic chemotherapy or two cycles of any hypomethylating agent-based therapy
• Refractory AML: =\< 2 prior induction regimens (example: patients who receive 7+3 followed by 5+2 would count as one induction regimen) or a minimum of two cycles of any hypomethylating agent-based therapy
• Treatment-naive AML: must be 75 years and older with de novo or secondary AML to be considered eligible
• Relapsed MDS: disease recurrence after CR, partial remission (PR) or hematologic improvement with bone marrow blasts \>= 5% who relapse after:
• Allogeneic hematopoietic stem cell transplant, or
• After four cycles of any hypomethylating agent-based therapy
• Refractory MDS: disease progression at any time after initiation of hypomethylating agent treatment or persistent bone marrow blasts \>= 5% despite a minimum of four cycles of hypomethylating agent therapy
• Untreated or previously treated therapy- related or secondary MDS
• Allowed prior allogeneic hematopoietic stem cell transplantation (allo-HCT) regardless of stem cell source; patients must be at least 3 months post allo-HCT (at time of treatment start); mismatched transplantations would be allowed
• Patients must be off systemic immunosuppressive medications \> 2 weeks prior to treatment start; if patients are in systemic corticosteroids and must be on a dose of prednisone 5 mg/day or less (or equivalent), then patients must be on this reduced dose for \> 1 week prior to treatment start; topical steroids are allowed
• If post allo-HCT, then patient must have baseline donor T cell chimerism of \>= 20% (from peripheral blood); evaluation can be made within 4 weeks of treatment start
• No limitations on prior therapies

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 2 weeks prior to treatment start or those who have not recovered from adverse events due to agents administered more than 2 weeks prior to treatment start
• Hydroxyurea is allowed for symptomatic leukocytosis if clinically necessary; a total white blood cell (WBC) count \< 25 x 10\^9/L prior to first dose of decitabine on trial is required; prior leukapheresis and/or prior or concurrent treatment with hydroxyurea to achieve this level are allowed
• Ongoing concurrent hormonal therapy is allowed
• Participants with known central nervous system (CNS) involvement with leukemia or who are receiving intrathecal chemotherapy for active CNS leukemia
• Those with a history of CNS involvement that has been completely treated and those who require intrathecal chemotherapy prophylaxis are eligible in the expansion cohorts
• Prior hypomethylating agent (HMA) therapy is allowed, however this study excludes patients with progression or relapse that occur while receiving HMA-based therapy within 12 weeks prior to treatment start on study; disease progression is defined as either: (1) patients with prior MDS who progress to AML (defined by the presence of \>= 20% blasts in peripheral blood or bone marrow) on HMA-based therapy; OR (2) patients with AML with evidence of progressive disease according to European Leukemia Net \[ELN\] 2017 criteria) (e.g. \> 50% increase in marrow blasts over baseline or \> 50% increase in peripheral blasts to \> 25 x 10\^9/L (\> 25,000/uL) (in absence of differentiation syndrome)
• (Note: Patients who relapse post-transplant who received HMA treatment prior to transplant are eligible for study)
• Donor lymphocyte infusion within 8 weeks prior to treatment start if post-transplant
• For patients that are post-transplant, ineligible patients include those with a history of overall grade III or IV (severe) acute GVHD at any time even if resolved
• Patients with a history of prior treatment with anti-CTLA-4, anti-PD 1 antibody, or anti-PDL1 antibody
• Participants who are receiving any other investigational agents
• Participants with known CNS involvement with leukemia or who are receiving intrathecal chemotherapy that is either prophylactic or therapeutic; history of CNS involvement that has been completely treated (no longer receiving intrathecal chemotherapy) will be allowed
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; any other prior or ongoing condition, in the opinion of the investigator, that could adversely affect the safety of the patient or impair the assessment of study results; as patients with AML and MDS are prone to infections, if patients are actively being treated with appropriate antibiotics or antifungal therapy with clinical evidence of infection control, then they will be considered eligible for study
• Autoimmune disease: Patients who are not eligible include those with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\]); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis); patients with a history of autoimmune disease (specifically including: diabetes mellitus, vitiligo, Hashimoto's thyroiditis) who are asymptomatic, do not require immune suppression or steroids, and do not have threatened vital organ function from these conditions may be considered after discussion with the principal investigator (PI)
• No concurrent active malignancies are allowed on study for \>= 2 years prior to treatment start with the exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or breast

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Penter L, Liu Y, Wolff JO, Yang L, Taing L, Jhaveri A, Southard J, Patel M, Cullen NM, Pfaff KL, Cieri N, Oliveira G, Kim-Schulze S, Ranasinghe S, Leonard R, Robertson T, Morgan EA, Chen HX, Song MH, Thurin M, Li S, Rodig SJ, Cibulskis C, Gabriel S, Bachireddy P, Ritz J, Streicher H, Neuberg DS, Hodi FS, Davids MS, Gnjatic S, Livak KJ, Altreuter J, Michor F, Soiffer RJ, Garcia JS, Wu CJ. Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease. Blood. 2023 Apr 13;141(15):1817-1830. doi: 10.1182/blood.2022018246.

  PMID: 36706355 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Decitabine; Injections; Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Dr. Jacqueline Garcia
• Organization: Dana Farber Cancer Institute

Jacqueline_Garcia@dfci.harvard.edu

617-632-1906

Study Officials

• Jacqueline S Garcia

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2016
• First Posted: September 7, 2016
• Study Start: September 5, 2017
• Primary Completion: October 24, 2022
• Study Completion (Estimated): August 19, 2026
• Last Updated: April 29, 2026
• Results First Posted: January 7, 2025

Record last verified: 2026-02

Locations

US (11)