A Phase I Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Immunoregulatory Activity, and Preliminary Antitumor Activity of Anti-Programmed-Death 1 (PD-1) Antibody (Nivolumab, BMS 936558) and the Combination of Nivolumab and Ipilimumab in Subjects With Relapsed or Refractory Hematologic Malignancy

Location:

Rochester, Minn.

Trial status:
Open for Enrollment
Why is this study being done?

The purpose of this study is to determine the side effects of treatment with Nivolumab alone and in combination with Ipilimumab in subjects with hematological malignancies and the dose that should be recommended for use in future studies.

Who is eligible to participate?

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) Performance of 0 or 1 - Subjects must have histological confirmation of relapsed or refractory hematologic malignancy - Subjects with non-Hodgkin's lymphoma or Hodgkin lymphoma must have at least one measureable lesion > 1.5 cm as defined by lymphoma response criteria. Tumor sites that are considered measureable must not have received prior radiation therapy - Subjects with Multiple Myeloma (MM) must have detectable disease as measured by presence of monoclonal immunoglobulin protein in a serum electrophoresis: IgG, IgA, IgM,(M-protein ≥ 0.5 g/dl or serum IgD M-protein ≥ 0.05 g/dl) or serum free-light chain or 24 hour urine with free light chain. Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma - Subjects with Chronic myelogenous leukemia (CML) must have evidence of the Philadelphia chromosome by polymerase chain reaction (PCR) or chromosome analysis - Life expectancy of at least 3 months - For subjects with lymphoma, either an archived Formalin fixed tissue block, or 7 to 15 slides of tumor sample for performance of correlative studies - Subjects must have received at least one prior chemotherapy regimen. Subjects must be off therapy for at least 3 weeks ( 2 weeks for oral agents) prior to Day 1 - Prior palliative radiation must have been completed at least 2 weeks prior to study Day 1 - Toxicities related to prior therapy must have returned to Grade 1 or less, except for alopecia. Peripheral neuropathy must be Grade 2 or less - Adequate bone marrow function defined as: - Absolute neutrophil count ≥ 1000/μl (stable off any growth factor within 1 week of study drug administration) - Hemoglobin ≥ 9 g/dL (transfusion to achieve this level is permitted) - Platelet count ≥ 50 X 1000/ μl (transfusion to achieve this level is not permitted) - Adequate renal parameters defined as: Creatinine clearance (CrCl) > 40 ml/min (Cockcroft-Gault formula) - Adequate hepatic parameters defined as: - Aspartate aminotransferase (AST) ≤ 3 x Upper limit of normal (ULN) - Alanine aminotransferase (ALT) ≤ 3 x ULN - Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's Syndrome, who must have total bilirubin < 3.0 mg/dL and direct bilirubin < 0.5 mg/dL) - Women of child bearing potential (WOCBP) must use highly effective methods of birth control for up to 18 weeks after the last dose of investigational product - Men and women ≥ 18 years of age Exclusion Criteria: - Subjects with myelodysplasia, polycythemia vera, idiopathic thrombocythemia, myelofibrosis, acute leukemias, CML, T cell lymphoblastic or Burkitt lymphoma acute leukemias - Subjects with a history of central nervous system involvement by hematologic malignancy or symptoms suggestive of central nervous system involvement - Subjects with concomitant second malignancies (except adequately treated nonmelanomatous skin cancers, carcinoma in situ of the breast, treated superficial bladder cancer or prostate cancer or in situ cervical cancers) are excluded unless a complete remission was achieved at least 3 years prior to study entry and no additional therapy is required or anticipated to be required during the study period - Subjects with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of syndrome that requires systemic corticosteroids or immunosuppressive medications, except for subjects with vitiligo, resolved childhood asthma/atopy or autoimmune thyroid disorders - A serious uncontrolled medical disorder or active infection which would impair the ability of the subject to receive protocol therapy or whose control may be jeopardized by the complications of this therapy - Prior therapy with an anti-Programmed death-1 (anti-PD-1), anti-Programmed death ligand 1 (anti-PD-L1), anti Programmed death ligand 2 (anti-PD-L2), anti-CD137 or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways) - Non-oncology vaccine therapies for prevention of infectious diseases [eg human papilloma virus (HPV) vaccine) within 4 weeks of study drug administration. The inactivated seasonal influenza vaccine can be given to subjects before treatment and while on therapy without restriction. Influenza vaccines containing live virus or other clinically indicated vaccinations for infectious diseases (ie, pneumovax, varicella, etc.] may be permitted; but must be discussed with the Sponsor's Medical Monitor and may require a study drug washout period prior to and after administration of vaccine - Prior organ allograft or allogeneic bone marrow transplantation - Positive for human immunodeficiency virus (HIV 1/2) or known acquired immunodeficiency syndrome (AIDS) - Positive tests for hepatitis B virus surface antigen (HBsAg), or antibody to hepatitis B core Antigen or hepatitis C virus antibody (confirmed by Western Blot) or hepatitis C Ribonucleic acid (RNA) in serum - Ejection fraction less than 45% in subjects with prior Anthracycline exposure - History of Grade 4 anaphylactic reaction to monoclonal antibody therapy - Women who are pregnant or breastfeeding - WOCBP who are unwilling or unable to use an acceptable method to minimize the risk of pregnancy for the entire study period and for at least 18 weeks after the last dose of investigational product

Last updated:
4/8/2014
NCT ID:
NCT01592370
IRB Number:
12-004166