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Study of Idarubicin, Cytarabine, and Nivolumab in Patients With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT02464657
Recruitment Status : Active, not recruiting
First Posted : June 8, 2015
Last Update Posted : May 13, 2019
Sponsor:
Collaborator:
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 tolerable dose of nivolumab that can be give in combination with idarubicin and cytarabine in patients with MDS and AML. The safety and effectiveness of this drug combination will also be studied.

This is an investigational study. Nivolumab is not FDA-approved or commercially available. Idarubicin is FDA-approved and commercially available for the treatment of patients with AML. Cytarabine is FDA approved and commercially available for treatment of patient with AML. The use of these drugs in combination is investigational. The study doctor can explain how the drugs are designed to work.

Up to 75 patients will take part in this study. All will be enrolled at MD Anderson.


Condition or disease Intervention/treatment Phase
Leukemia Acute Myeloid Leukemia Myelodysplastic Syndrome Drug: Nivolumab Drug: Idarubicin Drug: Cytarabine Drug: Solu-medrol Drug: Dexamethasone Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Idarubicin, Cytarabine, and Nivolumab in Patients With High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
Actual Study Start Date : July 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Experimental: Nivolumab + Idarubicin + Cytarabine

Phase I starting dose of Nivolumab 1 mg/kg by vein on Day 24 of a 28 day cycle. Dose of Nivolumab escalated in successive cohorts of patients. After 2 cycles, if the disease appears to get better, participants receive Nivolumab by vein about every 2 weeks for up to 1 year.

Phase I and Phase II dose of Idarubicin 12 mg/m2 by vein daily for 3 on Days 1 - 3 of a 28 day cycle.

Phase I and Phase II dose of Cytarabine (Ara-C) 1.5 g/m2 by vein daily on Days 1 - 4 of a 28 day cycle.

Phase I and Phase II dose of Solumedrol 50 mg or Dexamethasone 10 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.

Phase II Starting Dose of Nivolumab: Maximum tolerated dose from Phase I.

Drug: Nivolumab

Phase I Starting Dose of Nivolumab: 1 mg/kg by vein on Day 24 of a 28 day cycle.

Phase II Starting Dose of Nivolumab: Maximum tolerated dose from Phase I.

Other Names:
  • BMS-936558
  • Opdivo

Drug: Idarubicin
Phase I and Phase II dose of Idarubicin 12 mg/m2 by vein daily for 3 on Days 1 - 3 of a 28 day cycle.
Other Name: Idamycin

Drug: Cytarabine
Phase I and Phase II dose of Cytarabine (Ara-C) 1.5 g/m2 by vein daily on Days 1 - 4 of a 28 day cycle.
Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

Drug: Solu-medrol
Phase I and Phase II dose of Solu-medrol 50 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.
Other Names:
  • Methylprednisolone
  • Depo-Medrol
  • Medrol

Drug: Dexamethasone
Phase I and Phase II dose of Dexamethasone 10 mg by vein daily for 3 - 4 days with Ara-C on Days 1 - 4 of a 28 day cycle.
Other Name: Decadron




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Nivolumab [ Time Frame: 28 days ]
    MTD is highest dose level in which <2 patients of 6 develop first cycle dose-limiting toxicity (DLT).


Secondary Outcome Measures :
  1. Event-Free Survival (EFS) [ Time Frame: 56 days ]
    EFS defined as time from the treatment start till treatment failure, relapse, or death whichever comes first. Treatment failure defined as not achieving complete response (CR) after two cycles of treatment.



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.


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

Inclusion Criteria:

  1. Diagnosis of 1) AML (WHO classification definition of >/= 20% blasts), or 2) high risk MDS (defined as the presence of 10% blasts).
  2. Patients aged 18 to 60 years are eligible. Patients older than 60 who are deemed fit to receive intensive chemotherapy by the treating physician are eligible after discussion with the PI.
  3. In the Phase I portion, patients with relapsed or refractory AML/MDS are also eligible, as per the treating physician's discretion.
  4. For the Phase II portion of the study, patients must be chemo-naive, i.e. not have received any prior chemotherapy (except hydrea or one dose of ara-C </= 2g) for AML or MDS. They could have received hypomethylator agents, transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or hydrea or one dose of ara-C </= 2g in order to safely control hyperleucocytosis prior to enrollment.
  5. Serum biochemical values with the following limits unless considered due to leukemia: ---Creatinine </= 1.5 mg/dl --- total bilirubin </= 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder --- transaminases (SG PT) </= 2.5 x ULN.
  6. Ability to take oral medication.
  7. Ability to understand and provide signed informed consent.
  8. Baseline test of ejection fraction must be >/= 50%.
  9. Performance status < 3, unless directly related to disease process as determined by the Principal Investigator.

Exclusion Criteria:

  1. Subjects with APL.
  2. Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results.
  3. Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study. --- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate 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 drug. --- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. --- Women must not be breastfeeding.
  4. Continued:Men who are sexually active with WOCBP must use acceptable birth control methods. Acceptable birth control methods include: oral or injectable hormonal birth control, intrauterine devices(IUDS), and double barrier methods (for example a condom in combination with spermicide). Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception.
  5. Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  6. History of cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within past 3 months.
  7. Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  8. Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of study drug.
  9. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  10. Active clinically serious and uncontrolled infection > CTCAE Grade 2 uncontrolled with antibiotics.
  11. Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
  12. Patients should be excluded if they are known to be positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
  13. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  14. History of allergy to study drug components.
  15. Prior immune checkpoint targeting drugs (e.g., anti PD1, and PDL1, anti-kir, anti CD137...etc)

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 ClinicalTrials.gov identifier (NCT number): NCT02464657


Locations
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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
Investigators
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Principal Investigator: Farhad Ravandi-Kashani, MD M.D. Anderson Cancer Center

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02464657     History of Changes
Other Study ID Numbers: 2014-0907
NCI-2015-01258 ( Registry Identifier: NCI CTRP )
First Posted: June 8, 2015    Key Record Dates
Last Update Posted: May 13, 2019
Last Verified: May 2019

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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:
Leukemia
Acute myeloid leukemia
AML
Myelodysplastic Syndrome
MDS
High-risk
Nivolumab
BMS-936558
Opdivo
Idarubicin
Idamycin
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride
Solu-Medrol
Methylprednisolone
Depo-Medrol
Medrol
Dexamethasone
Decadron

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Dexamethasone
Dexamethasone acetate
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Nivolumab
Idarubicin
Prednisolone hemisuccinate
Prednisolone phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents