Description:
This phase II trial studies the side effects of nivolumab and/or ipilimumab with or without
azacitidine and to see how well they work in treating patients with myelodysplastic syndrome.
Monoclonal antibodies, such as nivolumab and ipilimumab, may block cancer growth in different
ways by targeting certain cells. Drugs used in chemotherapy, such as azacitidine, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving nivolumab and/or ipilimumab
with or without azacitidine may work better in treating myelodysplastic syndrome.
Title
- Brief Title: Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome
- Official Title: Combination of Nivolumab and Ipilimumab With 5-Azacitidine in Patients With Myelodysplastic Syndromes (MDS)
Clinical Trial IDs
- ORG STUDY ID:
2014-0930
- SECONDARY ID:
NCI-2015-01494
- SECONDARY ID:
2014-0930
- SECONDARY ID:
P30CA016672
- NCT ID:
NCT02530463
Conditions
- Leukemia
- Myelodysplastic Syndrome
- Recurrent Myelodysplastic Syndrome
Interventions
| Drug | Synonyms | Arms |
|---|
| Azacitidine | 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza | Cohort IV (azacitidine, nivolumab) |
| Ipilimumab | Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy | Cohort II (ipilimumab) |
| Nivolumab | BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo | Cohort I (nivolumab) |
Purpose
This phase II trial studies the side effects of nivolumab and/or ipilimumab with or without
azacitidine and to see how well they work in treating patients with myelodysplastic syndrome.
Monoclonal antibodies, such as nivolumab and ipilimumab, may block cancer growth in different
ways by targeting certain cells. Drugs used in chemotherapy, such as azacitidine, work in
different ways to stop the growth of cancer cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Giving nivolumab and/or ipilimumab
with or without azacitidine may work better in treating myelodysplastic syndrome.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the safety of nivolumab and ipilimumab, as single agents or in combination
and with 5-azacitidine (azacitidine), in patients with myelodysplastic syndrome (MDS).
SECONDARY OBJECTIVES:
I. To explore the clinical activity of nivolumab and ipilimumab, as single agents or in
combination and with 5-azacitidine, in patients with MDS.
II. To explore the biological activity of these compounds in patients with MDS.
OUTLINE: Patients are assigned to 1 of 6 cohorts. Patients with hypomethylating failure MDS
are assigned to cohorts I, II, or III. Patients with previously untreated MDS are assigned to
cohorts IV, V, or VI.
COHORT I (COHORT COMPLETED AS OF 10/7/19): Patients receive nivolumab intravenously (IV) over
30 minutes on days 1 and 15. Treatment repeats every 4 weeks for up to 6 cycles in the
absence of disease progression or unacceptable toxicity. Patients with disease progression
may receive nivolumab and azacitidine at the discretion of the treating physician.
COHORT II (COHORT COMPLETED AS OF 10/7/19): Patients receive ipilimumab IV over 30 minutes on
day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable
toxicity. Patients with disease progression may receive ipilimumab and azacitidine at the
discretion of the treating physician.
COHORT III: Patients receive nivolumab IV over 30 minutes on days 1 and 15 and ipilimumab IV
over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 4 cycles in the absence
of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30
minutes every 2 weeks (or every 4 weeks if patients receive azacitidine) in the absence of
disease progression or unacceptable toxicity. Patients with disease progression may receive
ipilimumab, nivolumab, and azacitidine at the discretion of the treating physician.
COHORT IV (COHORT COMPLETED AS OF 10/7/19): Patients receive azacitidine IV over 10-40
minutes on days 1-5 and nivolumab IV over 30 minutes on days 6 and 20. Cycles repeat every 4
weeks in the absence of disease progression or unacceptable toxicity.
COHORT V: Patients receive azacitidine IV over 10-40 minutes on days 1-5 and ipilimumab IV
over 30 minutes on day 6. Cycles repeat every 4 weeks in the absence of disease progression
or unacceptable toxicity.
COHORT VI (COHORT ON-HOLD AS OF 10/7/19): Patients receive azacitidine IV over 10-40 minutes
on days 1-5 and nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 6.
Treatment with ipilimumab repeats every 4 weeks for 4 cycles in the absence of disease
progression or unacceptable toxicity. Cycles with nivolumab and azacitidine repeat every 4
weeks in the absence of disease progression or unacceptable toxicity.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Cohort I (nivolumab) | Experimental | Patients receive nivolumab IV over 30 minutes on days 1 and 15. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with disease progression may receive nivolumab and azacitidine at the discretion of the treating physician. | |
| Cohort II (ipilimumab) | Experimental | Patients receive ipilimumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease progression may receive ipilimumab and azacitidine at the discretion of the treating physician. | |
| Cohort III (nivolumab, ipilimumab) | Experimental | Patients receive nivolumab IV over 30 minutes on days 1 and 15 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes every 2 weeks (or every 4 weeks if patients receive azacitidine) in the absence of disease progression or unacceptable toxicity. Patients with disease progression may receive ipilimumab, nivolumab, and azacitidine at the discretion of the treating physician. | |
| Cohort IV (azacitidine, nivolumab) | Experimental | Patients receive azacitidine IV over 10-40 minutes on days 1-5 and nivolumab IV over 30 minutes on days 6 and 20. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | |
| Cohort V (azacitidine, ipilimumab) | Experimental | Patients receive azacitidine IV over 10-40 minutes on days 1-5 and ipilimumab IV over 30 minutes on day 6. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | |
| Cohort VI (azacitidine, nivolumab, ipilimumab) | Experimental | Patients receive azacitidine IV over 10-40 minutes on days 1-5 and nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 6. Treatment with ipilimumab repeats every 4 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Cycles with nivolumab and azacitidine repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | - Azacitidine
- Ipilimumab
- Nivolumab
|
Eligibility Criteria
Inclusion Criteria:
- Patients with MDS (up to 20% blasts) of any risk as defined as:
- Previously untreated
- Previously treated with hypomethylating agent (HMA) agent; patients need to have
relapsed or progressed after any number of cycles of HMA therapy; patients that
do not respond to HMA therapy will also be allowed in the study; relapse or
progression will be measured by International Working Group (IWG) 2006 criteria;
no response will be lack of clinical benefit after at least 6 cycles of HMA
therapy
- Creatinine =< 2.0 x upper limit of normal (ULN)
- Serum bilirubin =< 2.0 x ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.0 x ULN
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotropin (beta-hCG) pregnancy test result within 24 hours prior to the
first dose of treatment and must agree to use an effective contraception method 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 drugs; 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 a period of 31 weeks after the last dose of
investigational drug
- Patients or their legally authorized representative must provide written informed
consent
Exclusion Criteria:
- Second malignancy currently requiring active therapy, except breast or prostate cancer
stable on or responding to endocrine therapy
- 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
- History of pneumonitis
- Patients who are on high dose steroid (equivalent of prednisone 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); patients with history of human
immunodeficiency virus (HIV) disease are also excluded from the study
- Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational
agents
- Females who are pregnant or lactating
- Prior treatment with allogeneic stem cell transplantation
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Response Rate (ORR) in MDS Participants with Hypomethylating Agent Failure |
| Time Frame: | 24 weeks |
| Safety Issue: | |
| Description: | Overall response rate (ORR) defined as complete response plus partial response (CR + PR) + hematological improvement (HI). |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | M.D. Anderson Cancer Center |
Trial Keywords
- Leukemia
- Myelodysplastic syndrome
- MDS
- Nivolumab
- BMS-936558
- Opdivo
- Ipilimumab
- Yervoy
- BMS-734016
- MDX010
- 5-azacitidine
- Azacitidine
- 5-AZA
- Vidaza
- 5-AZC
- AZA-CR
- Ladakamycin
- NSC-102816
- Azacytidine
Last Updated
January 15, 2021
