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

NCT ID: NCT03417154

Last Updated: 2023-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-13
• Study Completion Date: 2022-01-25

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.

Conditions

Acute Myeloid Leukemia; Higher Risk Myelodysplastic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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.

Low dose Cyclophosphamide (CTX) Daily

Intervention Type: DRUG

Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment

Arm 2: Nivolumab every 2 weeks and Cyclophosphamide every 7 days

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

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.

Low dose Cyclophosphamide (CTX) Every 7 Days

Intervention Type: DRUG

Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment

Interventions

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.

Intervention Type: DRUG

Low dose Cyclophosphamide (CTX) Daily

Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment

Intervention Type: DRUG

Low dose Cyclophosphamide (CTX) Every 7 Days

Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment

Intervention Type: DRUG

Other Intervention Names

Opdivo; CTX; CTX

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fiona He, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Hematology, Oncology and Transplantation, Masonic Cancer Center

Locations

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HM2017-33

Identifier Type: OTHER

Identifier Source: secondary_id

2017LS116

Identifier Type: -

Identifier Source: org_study_id