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

Status
Active
Cancer Type
Leukemia
Myelodysplastic Syndromes (MDS)
Trial Phase
Phase I
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT02890329
Protocol IDs
10026 (primary)
17-718
10026
NCI-2016-01326
Study Sponsor
Dana-Farber - Harvard Cancer Center LAO

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.

Objectives

PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of combination decitabine and ipilimumab for relapsed or refractory myelodysplastic syndrome (MDS) or relapsed or refractory acute myeloid leukemia (AML) in patients who are post allogeneic hematopoietic stem cell transplant (allo-HCT).
II. 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.

SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity.
II. To determine the overall response rate (ORR) including complete remission (CR) and complete remission with incomplete count recovery (CRi) for AML following 2003 International Working Group (IWG) response criteria.
III. To determine the ORR including CR, partial remission, marrow CR, hematologic improvement for MDS using 2006 IWG criteria.
IV. To determine the overall survival and progression free survival at 1 year.
V. To determine the duration of remission.
VI. To capture the incidence and severity of acute graft-versus-host disease (GVHD) in the post allo-HCT cohort.
VII. To capture the incidence and severity of chronic graft-versus-host disease (GVHD) in the post allo-HCT cohort.

EXPLORATORY OBJECTIVES:
I. To measure the absolute lymphocyte count (ALC) prior to treatment and during treatment.
II. 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.
III. To evaluate the histopathologic findings of immune response using immunohistochemistry.
IV. To determine the immune response in the AML tumor microenvironment by using flow cytometry and single cell mass cytometry to evaluate T cell subsets.

OUTLINE: This is a dose-escalation study of ipilimumab.

ARM A (PATIENTS POST ALLO-HCT):
PRIMING PHASE: Patients receive decitabine intravenously (IV) over 60 minutes on days 1-5 out of 28 days.

INDUCTION PHASE: 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: 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.

ARM B (TRANSPLANT NAIVE PATIENTS):
PRIMING PHASE: Patients receive decitabine IV over 60 minutes on days 1-5 out of 28 days.

INDUCTION PHASE: 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: 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.

After completion of study treatment, patients are followed up every 3 months for up to 52 weeks (1 year).

Eligibility

  1. 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
  2. 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
  3. 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
  4. 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
  5. No limitations on prior therapies
  6. Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  7. 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
  8. Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT) =< 3.0 x local institutional ULN
  9. Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase (SGPT) =< 3.0 x local institutional ULN
  10. Serum creatinine =< 2.0 x local institutional ULN
  11. 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 study drug administration
  12. 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
  13. Ability to understand and the willingness to sign a written informed consent document

Treatment Sites in Georgia

Atlanta Cancer Care - Conyers


1498 Klondike Road
Suite 106
Conyers, GA 30094
404-303-3355
www.atlantacancercare.com

Atlanta Cancer Care - Stockbridge


7813 Spivey Station Boulevard
Suite 210
Jonesboro, GA 30236
678 466-2069
www.atlantacancercare.com

Atlanta Cancer Care - Tower


5670 Peachtree Dunwoody Road
Suite 1100
Atlanta, GA 30342
404-303-3355
www.atlantacancercare.com

Atlanta Gynecologic Oncology


980 Johnson Ferry Road
Suite 900
Atlanta, GA 30342
404-303-3355
www.geraldfeuer.com

Georgia Cancer Specialists - Athens


125 King Avenue
Suite 200
Athens, GA 30606
www.gacancer.com

Georgia Cancer Specialists - Canton


228 Riverstone Drive
Canton, GA 30114
www.gacancer.com

Georgia Cancer Specialists - CenterPointe


1100 Johnson Ferry Road
Suite 600
Sandy Springs, GA 30342
404-256-4777 ext 9242
www.gacancer.com

Georgia Cancer Specialists - Kennestone


790 Church Street
Suite 335
Marietta, GA 30060
www.gacancer.com

Georgia Cancer Specialists - Macon-Coliseum


308 Coliseum Drive
Suite 120
Macon, GA 31217
478-745-6130 x8152
www.gacancer.com

Georgia Cancer Specialists - Stemmer


2712 Lawrenceville Highway
Decatur, GA 30033
770-496-5555
www.gacancer.com

Georgia Gynecologic Oncology


980 Johnson Ferry Road
Suite 910
Atlanta, GA 30342
404-303-3355
www.ggo-atl.com/

Northside Hospital Cancer Institute


1000 Johnson Ferry Road NE
Atlanta, GA 30342
404-303-3355
www.northside.com

Northside Hospital Cancer Institute - Forsyth


1200 Northside Forsyth Drive
Suite 140
Cumming, GA 30041
404-303-3355
www.northside.com

University Gynecologic Oncology


960 Johnson Ferry Road
Suite 130
Atlanta, GA 30342
404-303-3355
www.ugynonc.com

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
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