Clinical Trial 19239

Cancer Type:
Interventions:Ipilimumab; Yervoy (Ipilimumab); decitabine (5-aza-2'-deoxycytidine)

Study Type: Treatment
Phase of Study: Phase I

  • Kendra Sweet


Study Title

A Phase 1 Study of Ipilimumab in Combination with Decitabine in Relapsed or Refractory Myelodysplastic Syndrome/Acute Myeloid Leukemia


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 or does not respond to treatment. Monoclonal antibodies, such as ipilimumab, may block cancer growth in different ways by targeting certain cells. 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.


1.1 Primary Objectives: To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of combination decitabine and ipilimumab for relapsed or refractory MDS or relapsed or refractory AML in patients who are post allogeneic hematopoietic stem cell transplant (allo-HCT). To determine the MTD or RP2D of combination decitabine and ipilimumab for relapsed or refractory MDS or relapsed or refractory AML in patients who are transplant naive. 1.2 Secondary Objectives: To observe and record anti-tumor activity. Although the clinical benefit of this novel combination has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. To determine the overall response rate (ORR) including complete remission (CR) and complete remission with incomplete count recovery (CRi) for AML following 2003 IWG response criteria [6]. To determine the ORR including CR, partial remission, marrow CR, hematologic improvement for MDS using 2006 IWG criteria [7]. To determine the overall survival and progression free survival at 1 year. To determine the duration of remission. To capture the incidence and severity of acute graft-versus-host disease (GVHD) in the post allo-HCT cohort. To capture the incidence and severity of chronic graft-versus-host disease (GVHD) in the post allo-HCT Cohort 1.3 Exploratory Objectives: To measure the absolute lymphocyte count (ALC) prior to treatment and during treatment. We will compare changes in ALC between responders and non-responders given evidence that ALC after two cycles may be a predictor of clinical response in solid tumors. To evaluate the genome for evidence of clonal evolution among longitudinal samples (prior to treatment, during treatment, and at relapse if relevant) from individual patients. We will compare leukemic genotypic patterns among responders and non-responders. To evaluate the histopathologic findings of immune response using immunohistochemistry. To determine the immune response in the AML tumor microenvironment by using flow cytometry and single cell mass cytometry to evaluate T cell subsets. We will evaluate cytokine and chemokine panels. We will further evaluate the gene expression patterns of immune infiltrates. We will evaluate for alterations in antigen presenting cells in response to decitabine and combination therapy. We will evaluate for resistance to immune response due to STAT3 activation.

Inclusion Criteria

  • Patients with evidence of relapsed or refractory acute myeloid leukemia (AML) or relapsed or refractory myelodysplastic syndrome (MDS)
  • 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.
  • For refractory AML: equal to or less than 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.
  • For treatment-naive AML: must be 75 years and older with de novo or secondary AML to be considered eligible.
  • For relapsed MDS: disease recurrence after complete remission (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.
  • For 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.
  • 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.
  • Participants 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status => Adequate hepatic and renal function.
  • Negative serum pregnancy test for women who are of child bearing potential; women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.
  • Patients with known active human immunodeficiency virus (HIV) infection; patients with chronic HIV with a CD4 > 250, undetectable viral load by PCR, without opportunistic infection, and on a stable regimen of highly active anti-retroviral therapy (HAART) therapy would be eligible.
  • Ability to understand and the willingness to sign a written informed consent document.

  • Exclusion Criteria

  • 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 during screening, lead in, and cycle 1 only if clinically necessary; a total white blood cell (WBC) count > Donor lymphocyte infusion within 8 weeks prior to treatment start if post-transplant
  • Prior history of severe (grade III or IV) acute GVHD even if resolved if post-transplant
  • History of prior treatment with anti-CTLA-4, anti-PD 1 antibody, or anti-PDL1 antibody
  • Receiving any other investigational agents
  • Known central nervous system (CNS) involvement with leukemia or 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; 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 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
  • Known active hepatitis B virus (HBV) infection should be excluded; however, if a patient has HBV history with an undetectable HBV load by polymerase chain reaction (PCR), no liver-related complications, and is on definitive HBV therapy, then he/she would be eligible for study
  • Known active hepatitis C virus (HCV) infection; patients with a history of HCV infection who received definitive therapy and has an undetectable viral load by PCR would be eligible
  • Women who are pregnant or breastfeeding