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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

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Higher Risk Myelodysplastic Syndrome Drug: Nivolumab Drug: Stage 1 Arm 1: Low dose Cyclophosphamide (CTX) Drug: Stage 1 Arm 2: Low dose Cyclophosphamide (CTX) Drug: Stage 2: Low dose Cyclophosphamide (CTX) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nivolumab and Oral Cyclophosphamide for Relapsed/Refractory Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndrome (MDS)
Actual Study Start Date : August 13, 2018
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2023


Arm Intervention/treatment
Experimental: Stage 1 Arms 1&2: Nivolumab and Cyclophosphamide 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

Experimental: Stage 2: Nivolumab and Cyclophosphamide 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 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




Primary Outcome Measures :
  1. Stage 1: Dosing Schedule of low-dose Cyclophosphamide [ Time Frame: 4 weeks from start of treatment ]
    Incidence of adverse events (AEs)

  2. 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.



Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 30 days from start of treatment ]
    Incidence of overall response.

  2. Progression Free Survival (PFS) [ Time Frame: 6 months from start of treatment ]
    Incidence of progression free survival.

  3. Overall Survival (OS) [ Time Frame: 6 months from start of treatment ]
    Incidence of overall survival.



Information from the National Library of Medicine

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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:

  • ≥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

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): NCT03417154


Contacts
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Contact: Amy Hays, RN 612-626-0461 hays0024@umn.edu
Contact: Fiona He, MD (612) 624-6982 fionahe@umn.edu

Locations
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United States, Minnesota
University of Minnesota Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Kim Nelson, RN    612-273-2925    knelso62@fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Fiona He, MD Division of Hematology, Oncology and Transplantation, Masonic Cancer Center

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03417154     History of Changes
Other Study ID Numbers: 2017LS116
HM2017-33 ( Other Identifier: University of Minnesota Division of Hematology, Oncology and Transplantation )
First Posted: January 31, 2018    Key Record Dates
Last Update Posted: December 28, 2018
Last Verified: December 2018

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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

Keywords provided by Masonic Cancer Center, University of Minnesota:
AML
MDS

Additional relevant MeSH terms:
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Nivolumab
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
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological