Lirilumab and Nivolumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)

NCT02599649 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0934NCI-2015-02120
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if lirilumab and Opdivo (nivolumab), alone or in combination with Vidaza (azacitidine), can help to control MDS. The safety of these drug combinations will also be studied. This is an investigational study. Lirilumab is not FDA approved or commercially available. It is currently being used for research purposes. Nivolumab is FDA approved and commercially available for the treatment of melanoma and non small cell lung cancer (NSCLC). Azacitidine is FDA approved and commercially available for the treatment of MDS. The study doctor can explain how the study drugs are designed to work. Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.

Conditions

Leukemia

Keywords

Myelodysplastic syndrome; MDS; Low or intermediate-1 MDS; High Risk MDS; Lirilumab; Nivolumab; BMS-936558; Opdivo; Azacitidine; 5-azacytidine; 5-aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816; Azacytidine

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall response rate (ORR) defined as complete response plus partial response (CR + PR) and hematological improvement (HI). MDS International Working Group criteria used to assess response.

  116 days

Study Arms (4)

Low or Intermediate-1 MDS Group - Lirilumab

EXPERIMENTAL

Lirilumab by vein over about 60 minutes 1 time each 28 day cycle.

Drug: Lirilumab

Low or Intermediate-1 MDS Group - Nivolumab + Lirilumab

EXPERIMENTAL

Nivolumab by vein over about 60 minutes every 2 weeks during Cycles 1-9. Lirilumab by vein over about 60 minutes 1 time each cycle. Cycle is 28 days.

Drug: Lirilumab; Drug: Nivolumab

High Risk MDS Group - Azacitidine + Lirilumab

EXPERIMENTAL

Azacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle.

Drug: Lirilumab; Drug: Azacitidine

High Risk MDS Group - Azacitidine + Lirilumab + Nivolumab

EXPERIMENTAL

Azacitidine by vein over about 60 minutes on Days 1-7 of each 28 day cycle. Lirilumab by vein over about 60 minutes on Day 7 of each 28 day cycle. On Days 7 and 21 of Cycles 1-9 and then on Day 7 of Cycles 10 and beyond, Nivolumab by vein over about 60 minutes.

Drug: Lirilumab; Drug: Nivolumab; Drug: Azacitidine

Interventions

Lirilumab DRUG

3 mg/kg by vein every 4 weeks.

High Risk MDS Group - Azacitidine + Lirilumab; High Risk MDS Group - Azacitidine + Lirilumab + Nivolumab; Low or Intermediate-1 MDS Group - Lirilumab; Low or Intermediate-1 MDS Group - Nivolumab + Lirilumab

Nivolumab DRUG

3 mg/kg by vein on Days 7 and 21 of a 28 day cycle.

Also known as: BMS-936558, Opdivo

High Risk MDS Group - Azacitidine + Lirilumab + Nivolumab; Low or Intermediate-1 MDS Group - Nivolumab + Lirilumab

Azacitidine DRUG

75 mg/m\^2 by vein for 7 days of a 28 day cycle.

Also known as: 5-azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Azacytidine

High Risk MDS Group - Azacitidine + Lirilumab; High Risk MDS Group - Azacitidine + Lirilumab + Nivolumab

Eligibility Criteria

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

You may qualify if:

• Patients with MDS (up to 20% blasts) of any risk. Patients with lower risk MDS (low and int-1 by IPSS) could have received prior non-hypomethylating agent therapy (ie growth factors or lenalidomide). Patients with higher risk MDS (int-2 or high by IPSS) should not have received prior therapy with a hypomethylating agent.
• Age 18 years or older.
• Adequate organ function: creatinine \</=2.5 x Upper Limit of Normal (ULN); serum bilirubin \</=2.5 x ULN; aspartate transaminase (AST) and alanine transaminase (ALT) \</=2.5 x ULN.
• Eastern Cooperative Oncology Group (ECOG) performance status \</=2.
• Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 24 hours prior to the first dose of treatment and must agree to use an effective contraception to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. Females of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
• Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 31 weeks after the last dose of nivolumab.
• Patients or their legally authorized representative must provide written informed consent.

You may not qualify if:

• History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses).
• Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 2 weeks prior to the first dose of the study drugs.
• Patients with any other known concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association (NYHA) Class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study.
• Patients unwilling or unable to comply with the protocol.
• Patients who are on high dose steroid (ie prednisone or equivalent more than 10 mg a day) or immune suppression medications.
• Patients with autoimmune diseases (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]).
• Patients with a history of Inflammatory Bowel Disease such as Crohn's disease and ulcerative colitis
• Patients known to be positive for hepatitis B surface antigen expression or with active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months) or with a history of HIV disease.
• Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents.
• Females who are pregnant or lactating
• Prior treatment with stem cell transplantation.
• Prohibited Prior Treatments and/or Therapies: a) Prior therapy with an anti-KIR, anti-PD-1, or anti-PD-L1, antibody. b) Prior treatment regimens with any immune cell modulating antibody such as anti-CD137 and anti-OX40. However, prior anti-CTLA4 therapy is allowed if the last dose is 101 days or more from the first dose of study drug. c) Exposure to any other investigational drug within 2 weeks prior to the first dose of study drug (within 101 days for anti-CTLA4 therapy). d) Any anti-cancer therapy (e.g., chemotherapy, biologics, vaccines, radiotherapy with curative intent, or hormonal treatment) within 2 weeks prior to the first dose of study drug administration (within 101 days for anti-CTLA4 therapy administration.
• Continued from #12: e) Use of non-oncology vaccines containing live virus for prevention of infectious diseases within 4 weeks prior to study drug. The use of the inactivated seasonal influenza vaccine (Fluzone®) is allowed. f) Systemic corticosteroid at immunosuppressive doses (\> 10 mg/day of prednisone or equivalent), must be discontinued at least 2 weeks prior to enrollment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Yalniz FF, Daver N, Rezvani K, Kornblau S, Ohanian M, Borthakur G, DiNardo CD, Konopleva M, Burger J, Gasior Y, Pierce S, Kantarjian H, Garcia-Manero G. A Pilot Trial of Lirilumab With or Without Azacitidine for Patients With Myelodysplastic Syndrome. Clin Lymphoma Myeloma Leuk. 2018 Oct;18(10):658-663.e2. doi: 10.1016/j.clml.2018.06.011. Epub 2018 Jun 15.

  PMID: 30001986 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

lirilumab; Nivolumab; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Guillermo Garcia-Manero, MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

ggarciam@mdanderson.org

713-745-3428

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 6, 2015
• Study Start: March 21, 2016
• Primary Completion: January 30, 2019
• Study Completion: January 30, 2019
• Last Updated: January 14, 2020
• Results First Posted: January 6, 2020

Record last verified: 2020-01

Locations

US (1)