Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02890329
Recruitment Status : Recruiting
First Posted : September 7, 2016
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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 or does not respond to treatment. 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 in treating patients with relapsed or refractory myelodysplastic syndrome or acute myeloid leukemia.

Condition or disease Intervention/treatment Phase
Blasts 5 Percent or More of Bone Marrow Nucleated Cells Hematopoietic Cell Transplantation Recipient Myelodysplastic Syndrome Previously Treated Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes Refractory Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Drug: Decitabine Biological: Ipilimumab Other: Laboratory Biomarker Analysis Phase 1

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Ipilimumab in Combination With Decitabine in Relapsed or Refractory Myelodysplastic Syndrome/Acute Myeloid Leukemia
Actual Study Start Date : April 14, 2017
Estimated Primary Completion Date : July 1, 2020
Estimated Study Completion Date : July 1, 2020


Arm Intervention/treatment
Experimental: Arm A (decitabine, ipilimumab)

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 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 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
Given IV
Other Names:
  • 5-Aza-2'-deoxycytidine
  • Aza-TdC
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies

Experimental: Arm B (decitabine, ipilimumab)

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 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 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
Given IV
Other Names:
  • 5-Aza-2'-deoxycytidine
  • Aza-TdC
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Maximum tolerated dose (recommended phase 2 dose) of ipilimumab in combination with decitabine [ Time Frame: Up to 56 days ]
    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.


Secondary Outcome Measures :
  1. Clinical response to treatment [ Time Frame: Up to 52 weeks ]
    Assessed by 2003 International Working Group criteria for acute myeloid leukemia and 2006 International Working Group criteria for myelodysplastic syndrome.

  2. Anti-leukemic activity described in terms of best overall response rate [ Time Frame: Up to 52 weeks ]
    Will be assessed by 2003 International Working Group response criteria for acute myeloid leukemia and 2006 International Working Group criteria for myelodysplastic syndrome. For acute myeloid leukemia, overall response rate includes complete remission + complete remission with incomplete count recovery; for myelodysplastic syndrome, overall response rate includes complete remission + marrow complete remission + partial remission + hematologic improvement.

  3. Anti-leukemic activity described in terms of progression free survival [ Time Frame: Time from registration to the earlier of progression or death due to any cause, assessed up to 52 weeks ]
    Will be assessed by 2003 International Working Group criteria for acute myeloid leukemia and 2006 International Working Group criteria for myelodysplastic syndrome. Time to event summaries will use the Kaplan-Meier method.

  4. Anti-leukemic activity described in terms of overall survival [ Time Frame: Time from registration to death due to any cause or censored at the date last known alive, assessed up to 52 weeks ]
    Will be assessed by 2003 International Working Group criteria for acute myeloid leukemia and 2006 International Working Group criteria for myelodysplastic syndrome. Time to event summaries will use the Kaplan-Meier method.

  5. Incidence of acute graft-versus-host disease [ Time Frame: Up to 100 days ]
    Will be separately evaluated in patients in the post-allogeneic hematopoietic stem cell transplant cohort, and compared to events with response to treatment. Graft-versus-host disease for the patients on the post-transplant arm will be estimated and reported with a 90% exact binomial confidence interval.

  6. Incidence of chronic graft-versus-host disease [ Time Frame: Up to 52 weeks ]
    Will be separately evaluated in patients in the post-allogeneic hematopoietic stem cell transplant cohort, and compared to events with response to treatment. Graft-versus-host disease for the patients on the post-transplant arm will be estimated and reported with a 90% exact binomial confidence interval.


Other Outcome Measures:
  1. Ability of absolute lymphocyte count to predict response [ Time Frame: Up to course 3 day 1 ]
    Absolute lymphocyte count levels will be divided into: low (< 1000 cells/ul) and normal/high (greater than or equal to 1000 cells/ul). The response and overall survival of patients with low absolute lymphocyte count versus normal/high absolute lymphocyte count will be compared using Kaplan-Meier estimates and the differences will be assessed using log-rank test.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with evidence of relapsed or refractory acute myeloid leukemia (AML) OR treatment naive AML who are 75 years or older OR relapsed or refractory myelodysplastic syndrome (MDS)

    • For subjects with 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 subjects with 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
    • For subjects with treatment-naive AML: must be 75 years and older with de novo or secondary AML to be considered eligible
    • For subjects with 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
    • For subjects with 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
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Total bilirubin =< 1.5 x local institutional upper limit of normal (ULN)

    • If elevated total bilirubin is due Gilbert's disease or disease-related hemolysis then total bilirubin =< 3.0 x local institutional ULN
  • Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT) =< 3.0 x local institutional ULN
  • Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT) =< 3.0 x local institutional ULN
  • Serum creatinine =< 2.0 x local institutional ULN
  • Negative serum pregnancy test for women who are of child bearing potential (test must be repeated if performed > 72 hours from treatment start); the effects of ipilimumab on the developing human fetus are unknown; for this reason and because immunotherapy agents as well as decitabine are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; 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 polymerase chain reaction (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 < 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
  • 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 x10^9/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 central nervous system (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
  • Patients with known active hepatitis B virus (HBV) infection should be excluded because of potential effects on immune function and/or drug interactions; 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
  • Patients with 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
  • Pregnant women are excluded from this study because ipilimumab has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ipilimumab, breastfeeding should be discontinued if the mother is treated with ipilimumab; these potential risks may also apply to decitabine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02890329


Locations
Layout table for location information
United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Site Public Contact    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Samer K. Khaled         
University of California Davis Comprehensive Cancer Center Active, not recruiting
Sacramento, California, United States, 95817
United States, Florida
Moffitt Cancer Center Active, not recruiting
Tampa, Florida, United States, 33612
United States, Massachusetts
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Site Public Contact    877-726-5130      
Principal Investigator: Jacqueline S. Garcia         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Site Public Contact    888-823-5923    ctsucontact@westat.com   
Principal Investigator: Jacqueline S. Garcia         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Site Public Contact    617-667-9925      
Principal Investigator: Jacqueline S. Garcia         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Site Public Contact    877-442-3324      
Principal Investigator: Jacqueline S. Garcia         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Site Public Contact    800-641-2422    CTUReferral@UHhospitals.org   
Principal Investigator: Benjamin K. Tomlinson         
United States, Virginia
University of Virginia Cancer Center Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Site Public Contact    434-243-6303    PAS9E@virginia.edu   
Principal Investigator: Michael K. Keng         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Jacqueline S Garcia Dana-Farber - Harvard Cancer Center LAO

Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02890329     History of Changes
Other Study ID Numbers: NCI-2016-01326
NCI-2016-01326 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-718
10026 ( Other Identifier: Dana-Farber - Harvard Cancer Center LAO )
10026 ( Other Identifier: CTEP )
UM1CA186709 ( U.S. NIH Grant/Contract )
First Posted: September 7, 2016    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: January 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Ipilimumab
Decitabine
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors