An Open-label Study of Lirilumab (BMS-986015) in Combination With 5-azacytidine (Vidaza) for the Treatment of Patients With Refractory/ Relapsed Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02399917
Recruitment Status : Completed
First Posted : March 26, 2015
Last Update Posted : July 30, 2018
Bristol-Myers Squibb
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to find the highest tolerated dose of the combination of lirilumab and 5-azacytidine that can be given to patients with AML or high-risk MDS. Researchers also want to learn if the drug combination can help to control the disease. The safety of the drug combination will also be studied.

This is an investigational study. Lirilumab is not FDA approved or commercially available. 5-azacytidine is FDA-approved and commercially available for the treatment of MDS, which can lead to AML, but it has not been approved for the treatment of AML. The use of these drugs in combination is investigational. The study doctor can explain how the drugs are designed to work.

Up to 64 participants will be enrolled in this study. All will take part at MD Anderson.

Condition or disease Intervention/treatment Phase
Leukemia Drug: 5-azacytidine Drug: Lirilumab Behavioral: Phone Call Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Phase II Study of Lirilumab (BMS-986015) in Combination With 5-azacytidine (Vidaza) for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia
Actual Study Start Date : April 20, 2015
Actual Primary Completion Date : July 12, 2018
Actual Study Completion Date : July 12, 2018

Arm Intervention/treatment
Experimental: 5-azacytidine + Lirilumab

5-azacytidine administered subcutaneously (SQ) or intravenously (IV) for 7 days of every cycle (Days 1-7) as determined by treating physician.

Lirilumab administered as 60 minute IV infusion on Day 8 (+/-2 days) of each 5-azacytidine cycle.

One cycle of therapy is defined as 28 days.

Phase I dose of lirilumab and 5-azacytidine depends on when participants joined study; Phase II doses begin at the highest dose tolerated in Phase I.

Drug: 5-azacytidine

Phase I Starting Dose: 75 mg/m2 a day by vein or subcutaneously on Days 1 - 7 of a 28 day cycle.

Phase II Starting Dose: Maximum tolerated dose (MTD) from Phase I.

Other Names:
  • Azacitidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Azacytidine

Drug: Lirilumab

Phase I Starting Dose: 1.0 mg/kg by vein on Day 8 of a 28 day cycle.

Phase II Starting Dose: Maximum tolerated dose (MTD) from Phase I.

Behavioral: Phone Call

If participant cannot come to the clinic, they will be called about 30 days after they go off study. This call will last about 5 minutes.

If participant goes off study for reasons other than the disease getting worse, they will be called every 3-6 months for up to 5 years. Each call should last about 5 minutes.

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of 5-azacytidine and Lirilumab [ Time Frame: 28 days ]

    MTD defined as the highest dose level with </= 1 out of 6 patients experience a dose limiting toxicity (DLT) during the first 28 days of treatment.

    DLT defined as clinically significant non-hematologic adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and occurring during the first cycle on study.

Secondary Outcome Measures :
  1. Overall response rate (ORR) of 5-azacytidine and Lirilumab [ Time Frame: 3 months ]
    Efficacy of the combination measured by the overall response rate (ORR), defined as CR (complete remission) + CRp (complete remission with incomplete platelet recovery) + CRi (complete remission with incomplete count recovery) + PR (partial response) + marrow clearance of blasts within 3 months of treatment initiation among adult patients with refractory/ relapsed AML. ORR and toxicity monitored simultaneously using the Bayesian approach of Thall, Simon, Estey (1995, 1996) and the extension by Thall and Sung (1998).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with AML or biphenotypic or bilineage leukemia who have failed at least one prior therapy. Patients with AML should have failed prior therapy or have relapsed after prior therapy.
  2. Patients should not be eligible or able to receive approved therapy of confirmed clinical benefit in this patient population.
  3. Patients with MDS or CMML who received therapy for the MDS or CMML and progress to AML are eligible at the time of diagnosis of AML regardless any prior therapy for AML. The WHO classification will be used for AML.
  4. Prior therapy with hydroxyurea, chemotherapy, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed
  5. Age >/=18 years
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2
  7. Adequate organ function: total bilirubin </= 2 times upper limit of normal (x ULN) (</= 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome); aspartate aminotransferase or alanine aminotransferase </= 2.5 x ULN (</= 5.0 x ULN if considered to be due to leukemic involvement); serum creatinine </= 2 x ULN or GFR>/=50
  8. Patients must provide written informed consent
  9. 9) In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and lirilumab will be at least 2 weeks OR at least 5 half-lives for cytotoxic/noncytotoxic agents. Use of one dose of cytarabine (up to 2 g/m2) is allowed prior to the start of study therapy or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and while the patient is on active study treatment, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted
  10. 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
  11. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment. The details of adequate method of contraception are shown in the protocol section 4.1.10 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

Exclusion Criteria:

  1. Patients with known allergy or hypersensitivity to lirilumab, 5-azacytidine, or any of their components. Patients who have previously been treated with lirilumab in combination with 5-azacytidine will be excluded.
  2. 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.
  3. Patients with a known history of any of the following autoimmune diseases are excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]).
  4. Patients with organ allografts (such as renal transplant) are excluded
  5. Patients with allogeneic stem cell transplantation within the last 6 months or patients with active GVHD will be excluded.
  6. Ongoing immunosuppressive therapy, including cyclosporine and tacrolimus. Patients who are on high dose steroid. Note: Subjects may be using systemic corticosteroids (daily doses </= 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids.
  7. Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia.
  8. Active and uncontrolled disease/(active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure NYHA class III/IV, clinically significant and uncontrolled arrhythmia) as judged by the treating physician.
  9. Patients with active and uncontrolled Human Immunodeficiency Virus (HIV) infection will be excluded. However, patients with well controlled HIV infection will be considered.
  10. Patients 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)
  11. 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
  12. Patients unwilling or unable to comply with the protocol.
  13. Pregnant or breastfeeding
  14. Acute promyelocytic leukemia (APL).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02399917

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bristol-Myers Squibb
Principal Investigator: Naval Daver, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02399917     History of Changes
Other Study ID Numbers: 2014-0862
NCI-2015-00678 ( Registry Identifier: NCI CTRP )
First Posted: March 26, 2015    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Acute Myeloid Leukemia
Myelodysplastic Syndrome (MDS).
Phone call

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors