Nivolumab and Oral Cyclophosphamide for R/R AML and HIgh Risk MDS
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ClinicalTrials.gov Identifier: NCT03417154 |
Recruitment Status :
Completed
First Posted : January 31, 2018
Last Update Posted : January 6, 2023
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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 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 12 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 |
Actual Primary Completion Date : | January 25, 2022 |
Actual Study Completion Date : | January 25, 2022 |

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 |
- Stage 1: Dosing Schedule of low-dose Cyclophosphamide [ Time Frame: 4 weeks from start of treatment ]Incidence of adverse events (AEs)
- 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.
- Objective Response Rate (ORR) [ Time Frame: 30 days from start of treatment ]Incidence of overall response.
- Progression Free Survival (PFS) [ Time Frame: 6 months from start of treatment ]Incidence of progression free survival.
- Overall Survival (OS) [ Time Frame: 6 months from start of treatment ]Incidence of overall survival.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

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
United States, Minnesota | |
University of Minnesota Masonic Cancer Center | |
Minneapolis, Minnesota, United States, 55455 |
Principal Investigator: | Fiona He, MD | Division of Hematology, Oncology and Transplantation, Masonic Cancer Center |
Responsible Party: | Masonic Cancer Center, University of Minnesota |
ClinicalTrials.gov Identifier: | NCT03417154 |
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: | January 6, 2023 |
Last Verified: | January 2023 |
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 |
AML MDS |
Preleukemia Myelodysplastic Syndromes Nivolumab Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute 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 Immune Checkpoint Inhibitors |