Clinical trial NCT03417154: Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS
Official title: Nivolumab and Oral Cyclophosphamide for Relapsed/Refractory Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndrome (MDS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Higher Risk Myelodysplastic Syndrome
Keywords: AML
MDS
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2018-01-31
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Stage 1: Dosing Schedule of Low-dose Cyclophosphamide
timeFrame: 4 weeks from start of treatment
measure: Clinical Benefit and Immunologic Response of the Combination Therapy
timeFrame: 90 days from start of treatment
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 30 days from start of treatment
measure: Progression Free Survival (PFS)
timeFrame: 6 months from start of treatment
measure: Overall Survival (OS)
timeFrame: 6 months from start of treatment
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
Study officials:
affiliation: Division of Hematology, Oncology and Transplantation, Masonic Cancer Center
name: Fiona He, MD
role: PRINCIPAL_INVESTIGATOR
References: