Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

NCT01757639 | Completed Phase 1 DMC

• 9 other identifiers: NCI-2012-02990NA_00076038J1276CDR00007445849214P30CA006973U01CA070095UM1CA186691UM1CA186704
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 9

Brief Summary

This phase I trial studies the side effects and best dose of ipilimumab and how well it works in treating patients with high-risk myelodysplastic syndrome or acute myeloid leukemia that has come back or no longer responds to treatment. Monoclonal antibodies, such as ipilimumab, may interfere with the ability of cancer cells to grow and spread.

Conditions

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Incidence of DLT of ipilimumab by grading and tabulation using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  42 days

• Changes in percentages of T-regs

  Changes in T-regs percentages at designated time points will be correlated with clinical responses and toxicity after ipilimumab. The response will be modeled as the vector for each individual from multiple measures of T-regs percentages as a function of time and group (MDS vs AML). T-regs percentages will be transformed onto the log-scale, and t tests will be used to compare groups at specific time points. Regression models that use generalized estimating equations will be implemented when all time points are considered to account for within-subject correlation of repeated measures.

  Baseline to up to 6 months post-treatment

Secondary Outcomes (7)

• Efficacy as defined by the International working group 2006 criteria for CR, PR, HI

  Up to 6 months post-treatment

• Progression free survival (PFS)

  From start of study to progression or death, assessed up to 6 months post-treatment

• Overall survival (OS)

  From start of study to death, assessed up to 6 months post-treatment

• Rate of prior use of demethylating agents

  Up to 6 months post-treatment

• Rate of pre-treatment CR

  Up to 6 months post-treatment

Study Arms (1)

Treatment (ipilimumab)

EXPERIMENTAL

INDUCTION: Patients receive ipilimumab IV on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning 12 weeks after last dose of induction ipilimumab, patients receive ipilimumab IV on day 1. Treatment repeats every 12 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis

Interventions

Ipilimumab BIOLOGICAL

Given IV

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

Treatment (ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Patients must be able to understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Life expectancy of greater than 6 months
• Must have one of the following diagnoses:
• Pathologically confirmed chronic myelomonocytic leukemia (CMML) or myelodysplastic syndromes (MDS) with high risk features at the time of referral for trial as defined by:
• Intermediate (INT)-2 or high International Prognostic Scoring System (IPSS) score
• Secondary MDS (defined as MDS developing in a patient with an antecedent hematologic disorder or any patient with prior chemotherapy or radiation exposure)
• INT-1 MDS with excess blasts (\>= 5% blasts in bone marrow \[BM\]) or red blood cell (RBC) transfusion-dependency
• MDS progressing to oligoblastic acute myeloid leukemia (AML) with 21-30% BM blasts
• CMML with \>= 5% marrow blasts, or RBC or platelet transfusion-dependency, abnormal karyotype, or proliferative features (white blood cell count \>=13,000/uL, splenomegaly on physical examination, or extramedullary disease)
• All patients are required to have failed to respond or relapsed after an initial response to hypomethylating agents 5-azacitidine or decitabine or have refused to receive hypomethylating therapy; failure to respond is defined as failing to achieve a CR, PR or HI after at least 4 cycles of hypomethylating therapy; these patients could have received other therapies or not, but must have received hypomethylating therapy or have refused to receive hypomethylating therapy
• Pathologically confirmed AML patients who have received one or two courses of induction chemotherapy or hypomethylating agent therapy AND no plans for further chemotherapy therapy, but remain with residual disease of \< 5% blasts in BM, by morphology, cytogenetics, fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR) or flow cytometry
• Patients must not have received any other treatment for their disease, including hematopoietic growth factors, within three weeks of beginning the trial, and should have recovered from all toxicities of prior therapy (to grade 0 or 1)
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry ECOG, or Karnofsky \>= 60%
• Calculated creatinine clearance by Modification of Diet in Renal Disease (MDRD) (CrCL) \> 50 ml/min/1.73 squared meter

You may not qualify if:

• Any serious medical condition, uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, laboratory abnormality, or psychiatric illness/social situations that would limit compliance with study requirements or prevent the subject from signing the informed consent form
• Pregnant or breast feeding females (lactating females must agree not to breast feed while taking ipilimumab)
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Use of any other experimental drug or therapy within 21 days of baseline
• Known hypersensitivity to ipilimumab or history of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab
• Prior use of ipilimumab, other cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blocking therapies, anti-programmed cell death 1 (PD 1) antibody, cluster of differentiation (CD) 137 agonist or other immune activating therapy such as anti-CD 40 antibody within the last 3 months of enrollment in the study; if any of these of these agents were used more than 3 months earlier to enrollment in study, the patient should have recovered from all toxicity and at least 3 months had passed since last use to allow for clearance and observation of any other side effects from the previous therapy
• Concurrent use of other anti-cancer agents or treatments, including other investigational agents
• 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 known immune impairment who may be unable to respond to anti-CTLA-4 antibody
• Patients with known evidence of active cancers, or other cancer under active treatment; exceptions include patients with no evidence of disease receiving adjuvant hormone-based therapy or either breast or prostate cancer
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections should be excluded because of potential effects on immune function and/ or possible drug interactions
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ipilimumab

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (9)

Yale University

New Haven, Connecticut, 06520, United States

Location

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University/Herbert Irving Cancer Center

New York, New York, 10032, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Texas Oncology at Baylor Irving Cancer Center

Irving, Texas, 75061, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

Ipilimumab; CTLA-4 Antigen

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• B. Smith

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2012
• First Posted: December 31, 2012
• Study Start: December 14, 2012
• Primary Completion: December 31, 2016
• Last Updated: March 21, 2018

Record last verified: 2017-11

Locations

US (9)