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

Acute Myeloid Leukemia Clinical Trial

Official title:

Nivolumab and Oral Cyclophosphamide for Relapsed/Refractory Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03417154
• Other study ID #: 2017LS116
• Secondary ID: HM2017-33
• Status: Completed
• Phase: Phase 2
• Start date: August 13, 2018
• Est. completion date: January 25, 2022

Study information

• Verified date: May 2023
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 25, 2022
• Est. primary completion date: January 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Higher Risk Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

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.
• Low dose Cyclophosphamide (CTX) Daily
Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment
• 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

Locations

Country	Name	City	State
United States	University of Minnesota Masonic Cancer Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Dosing Schedule of Low-dose Cyclophosphamide	Number of participants with adverse events	4 weeks from start of treatment
Primary	Clinical Benefit and Immunologic Response of the Combination Therapy	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.; Complete Remission (CR) - subjects must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state, an ANC > 1 x 109/L and platelet count = 100 x 109/L and normal marrow differential with < 5% blasts, and they will be RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). There should be no evidence of extramedullary leukemia; Complete Remission with Incomplete Hematologic Recovery (CRi) - subjects must fulfill all the criteria for CR except for incomplete hematological recovery; Complete Remission with Incomplete Platelet Recovery (CRp) - subjects must achieve CR except for incomplete platelet recovery; Partial Remission (PR) - subjects must have =50% bone marrow blast reduction or decrease to 5 to 25%	90 days from start of treatment
Secondary	Objective Response Rate (ORR)	Incidence of overall response.	30 days from start of treatment
Secondary	Progression Free Survival (PFS)	Incidence of progression free survival.	6 months from start of treatment
Secondary	Overall Survival (OS)	Incidence of overall survival.	6 months from start of treatment