Nivolumab and Ipilimumab After Donor Stem Cell Transplant in Treating Patients With High Risk Refractory or Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome

NCT03600155 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2017-0349NCI-2018-01450P30CA016672
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies the side effects and best dose of nivolumab and ipilimumab after donor stem cell transplant in treating patients with high risk acute myeloid leukemia or myelodysplastic syndrome that does not respond to treatment or has come back. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation Recipient

Outcome Measures

Primary Outcomes (1)

• Optimal dose of nivolumab in combination with ipilimumab

  Dose-finding will be carried out using the Bayesian optimal interval design.

  Up to day 42

Secondary Outcomes (4)

• Overall response rate (ORR)

  Up to 1 year

• Duration of response (DOR)

  From the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, assessed up to 1 year

• Disease-free survival (DFS)

  From the date of first dose of study drug until the date of documented graft versus host disease (GVHD), relapses from CR, or death from any cause, assessed up to 1 year

• Overall survival (OS)

  From the first dose of study drug until death or last follow-up, assessed up to 1 year

Other Outcomes (7)

• Neo-antigen identification

  Up to 1 year

• Immune cell phenotype

  Up to 1 year

• Immune checkpoint molecule expression

  Up to 1 year

Study Arms (3)

Arm A (nivolumab)

EXPERIMENTAL

Beginning at least 6 weeks post-stem cell transplant, patients receive nivolumab IV over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab

Arm B (ipilimumab)

EXPERIMENTAL

Beginning at least 6 weeks post-stem cell transplant, patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab

Arm C (nivolumab and ipilimumab)

EXPERIMENTAL

Beginning at least 6 weeks post-stem cell transplant, patients receive nivolumab IV over 60 minutes on days 1, 14, and 28, and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab

Interventions

Ipilimumab BIOLOGICAL

Given IV

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

Arm B (ipilimumab); Arm C (nivolumab and ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (nivolumab); Arm C (nivolumab and ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Patients with evidence of relapsed or refractory AML or MDS following allogeneic stem cell transplantation
• Patients must have received preparative regimens to include either busulfan- or melphalan-based regimens
• Patient must have achieved myeloid engraftment as defined by an absolute neutrophil count \>= 500 micro/L on 3 consecutive days
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Total bilirubin =\< 2 times upper limit of normal (x ULN) (=\< 3 x ULN if considered to be due to Gilbert's syndrome)
• Aspartate aminotransferase or alanine aminotransferase =\< 2.5 x ULN
• Serum creatinine =\< 2 x ULN or glomerular filtration rate (GFR) \>= 50
• Patients must provide written informed consent
• The interval from the infusion of stem cells to time of initiation of nivolumab or ipilimumab will be at least 6 weeks (42 days)
• Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
• Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

You may not qualify if:

• Patients with known allergy or hypersensitivity to nivolumab or ipilimumab or any of their components
• Patients with acute GVHD \> grade 2 at any time during the post-transplant course
• Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating physician
• Patients with a known history of any of the following autoimmune diseases are excluded:
• Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis)
• Patients with a history of rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis)
• Patients with solid organ allografts (such as renal transplant) are excluded
• Ongoing immunosuppressive therapy for the treatment of GVHD. Patients receiving GVHD prophylaxis will be allowed on this study
• Patients with symptomatic central nervous system (CNS) leukemia at the time of evaluation or patients with poorly controlled CNS leukemia
• Active and uncontrolled disease/(active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association \[NYHA\] class III/IV, clinically significant and uncontrolled arrhythmia) as judged by the treating physician
• Patients with known human immunodeficiency virus seropositivity will be excluded
• Known to be positive for hepatitis B by surface antigen expression. Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months)
• Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
• Patients unwilling or unable to comply with the protocol
• Pregnant or breastfeeding

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gheath Al-Atrash

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 16, 2018
• First Posted: July 26, 2018
• Study Start: October 11, 2018
• Primary Completion: December 2, 2024
• Study Completion: December 2, 2024
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

US (1)