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Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS

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ClinicalTrials.gov Identifier: NCT03417154
Recruitment Status : Recruiting
First Posted : January 31, 2018
Last Update Posted : December 28, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE January 2, 2018
First Posted Date  ICMJE January 31, 2018
Last Update Posted Date December 28, 2018
Actual Study Start Date  ICMJE August 13, 2018
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
  • Stage 1: Dosing Schedule of low-dose Cyclophosphamide [ Time Frame: 4 weeks from start of treatment ]
    Incidence of adverse events (AEs)
  • Stage 2: Clinical benefit and immunologic response of the combination therapy [ Time Frame: 90 days from start of treatment ]
    Overall response rate at 90 days from treatment start. Response is defined as CR + CRi + CRp + PR in AML and CR/PR/hematologic improvement (HI) in MDS.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03417154 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2018)
  • Objective Response Rate (ORR) [ Time Frame: 30 days from start of treatment ]
    Incidence of overall response.
  • Progression Free Survival (PFS) [ Time Frame: 6 months from start of treatment ]
    Incidence of progression free survival.
  • Overall Survival (OS) [ Time Frame: 6 months from start of treatment ]
    Incidence of overall survival.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS
Official Title  ICMJE Nivolumab and Oral Cyclophosphamide for Relapsed/Refractory Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndrome (MDS)
Brief Summary This is a phase II trial of nivolumab and low dose cyclophosphamide (CTX) when given in combination to patients with relapsed/refractory acute myeloid leukemia (AML) and higher-risk myelodysplastic syndrome (MDS) who are not eligible for or decline hematopoietic stem cell transplant. It includes a randomized pilot sub-study during stage 1.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Higher Risk Myelodysplastic Syndrome
Intervention  ICMJE
  • Drug: Nivolumab
    3mg/kg IV (or if prior alloHSCT, 1 mg/kg) over 30 minutes every 14 days on Days 1 and 15 for up to four 28-day courses.
    Other Name: Opdivo
  • Drug: Stage 1 Arm 1: Low dose Cyclophosphamide (CTX)
    Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment
    Other Name: CTX
  • Drug: Stage 1 Arm 2: Low dose Cyclophosphamide (CTX)
    Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment
    Other Name: CTX
  • Drug: Stage 2: Low dose Cyclophosphamide (CTX)
    Stage 2: Oral cyclophosphamide as assigned for up to 4 treatment courses with each treatment course equal to 28 days.
    Other Name: CTX
Study Arms  ICMJE
  • Experimental: Stage 1 Arms 1&2: Nivolumab and Cyclophosphamide
    Interventions:
    • Drug: Nivolumab
    • Drug: Stage 1 Arm 1: Low dose Cyclophosphamide (CTX)
    • Drug: Stage 1 Arm 2: Low dose Cyclophosphamide (CTX)
  • Experimental: Stage 2: Nivolumab and Cyclophosphamide
    Interventions:
    • Drug: Nivolumab
    • Drug: Stage 2: Low dose Cyclophosphamide (CTX)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 29, 2018)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2023
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ≥18 years of age
  • Meets one of the following disease criteria:

    • Primary (de novo) AML or higher-risk MDS with induction failure: No CR after 2 or more induction attempts with high dose chemotherapy or hypomethylating agents or other agents; no CR after 1 induction attempt and not eligible for a 2nd induction.. Higher risk MDS defined as risk score > 4.5 based on the revised IPSS criteria.
    • Secondary AML (from antecedent hematologic malignancy or treatment-related): Not in CR after 1 or more cycles of chemotherapy.
    • Relapsed AML: Blasts ≥5% in bone marrow or peripheral blood after prior attainment of CR; relapse at any time but currently ≥100 days following allogeneic HCT.
    • Relapsed MDS: Morphologic evidence of relapse or increase in blasts ≥5% in bone marrow or peripheral blood after prior attainment of hematologic improvement; or partial or complete response ; relapse at any time but currently ≥100 days following allogeneic HCT..
  • ECOG Performance Status ≤ 2 - refer to Appendix II
  • Adequate organ function within 14 days of study registration defined as:

    • Absolute Lymphocyte Count: ≥ 500 cells/mm3
    • Hepatic: total bilirubin ≤ 3 x upper limit of institutional normal (ULN); ALT and AST ≤ 5 x ULN
    • Renal: Serum creatinine ≤ 2 mg/dL
    • Pulmonary: No oxygen requirement on room air or requiring ≤ 2L supplemental O2
  • Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and continuing (23 weeks for females, 31 weeks for males) after the last dose of nivolumab
  • Voluntary written consent

Exclusion Criteria:

  • Pregnant or breastfeeding -The agents used in this study fall under Pregnancy Category D - Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days of study drug administration.
  • Prior allogeneic hematopoietic stem cell transplantation within previous 100 days (note patients with a prior alloHSCT receive nivolumab at the reduced dose of 1 mg/kg)
  • Signs or symptoms of active graft versus host disease
  • Active pneumonitis or uncontrolled infection
  • Received chemotherapy drugs within previous 2 weeks
  • Estimated life expectancy <28 days in the opinion of the enrolling investigator
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amy Hays, RN 612-626-0461 hays0024@umn.edu
Contact: Fiona He, MD (612) 624-6982 fionahe@umn.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03417154
Other Study ID Numbers  ICMJE 2017LS116
HM2017-33 ( Other Identifier: University of Minnesota Division of Hematology, Oncology and Transplantation )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fiona He, MD Division of Hematology, Oncology and Transplantation, Masonic Cancer Center
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP