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

NCT03417154 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2017LS116HM2017-33
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

AML; MDS

Outcome Measures

Primary Outcomes (2)

• Stage 1: Dosing Schedule of Low-dose Cyclophosphamide

  Number of participants with adverse events

  4 weeks from start of treatment

• 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 Outcomes (3)

• Objective Response Rate (ORR)

  30 days from start of treatment

• Progression Free Survival (PFS)

  6 months from start of treatment

• Overall Survival (OS)

  6 months from start of treatment

Study Arms (2)

Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily

EXPERIMENTAL

Drug: Nivolumab; Drug: Low dose Cyclophosphamide (CTX) Daily

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

EXPERIMENTAL

Drug: Nivolumab; Drug: Low dose Cyclophosphamide (CTX) Every 7 Days

Interventions

Nivolumab 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.

Also known as: Opdivo

Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily; Arm 2: Nivolumab every 2 weeks and Cyclophosphamide every 7 days

Low dose Cyclophosphamide (CTX) Daily DRUG

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

Also known as: CTX

Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily

Low dose Cyclophosphamide (CTX) Every 7 Days DRUG

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

Also known as: CTX

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Nivolumab; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Joseph Maakaron
• Organization: University of Minnesota, Masonic Cancer Center

maaka001@umn.edu

(612) 626-5654

Study Officials

• Fiona He, MD

  Division of Hematology, Oncology and Transplantation, Masonic Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 31, 2018
• Study Start: August 13, 2018
• Primary Completion: January 25, 2022
• Study Completion: January 25, 2022
• Last Updated: May 26, 2023
• Results First Posted: May 26, 2023

Record last verified: 2023-05

Locations

US (1)