Acute Myeloid LeukemiaPhase 2NCT03417154

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

A Phase 2 study testing Nivolumab, Low dose Cyclophosphamide (CTX) Daily and Low dose Cyclophosphamide (CTX) Every 7 Days in people with Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Myeloid Leukemia, Higher Risk Myelodysplastic Syndrome
What is being tested?: Nivolumab, Low dose Cyclophosphamide (CTX) Daily and Low dose Cyclophosphamide (CTX) Every 7 Days
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 1 siteUnited States
Study dates: 13 Aug 2018to 25 Jan 2022
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

≥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..

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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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, 55455

Other trials in United States

About this study

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

Conditions: Acute Myeloid Leukemia, Higher Risk Myelodysplastic Syndrome
Being tested: Nivolumab, Low dose Cyclophosphamide (CTX) Daily, Low dose Cyclophosphamide (CTX) Every 7 Days
Keywords: AML, MDS
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo
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) DailyDrug
Also called CTX
Oral cyclophosphamide 50mg + nivolumab 3 mg/kg IV every 2 weeks for up to 4 courses of treatment
Low dose Cyclophosphamide (CTX) Every 7 DaysDrug
Also called CTX
Oral cyclophosphamide 350 mg every 7 days + nivolumab 3mg/kg IV every 2 weeks for up to 4 courses of treatment

Study groups in NCT03417154
Study group	Role	What they receive
Arm 1: Nivolumab every 2 weeks and Cyclophosphamide daily	Experimental	Not described Receives: Drug: Nivolumab; Drug: Low dose Cyclophosphamide (CTX) Daily
Arm 2: Nivolumab every 2 weeks and Cyclophosphamide every 7 days	Experimental	Not described Receives: Drug: Nivolumab; Drug: Low dose Cyclophosphamide (CTX) Every 7 Days

What is being measured

The primary outcome is the main question the study is designed to answer.

Stage 1: Dosing Schedule of Low-dose Cyclophosphamide
Number of participants with adverse events
Measured: 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%
Measured: 90 days from start of treatment

Secondary outcomes (3)

Objective Response Rate (ORR)
Incidence of overall response.
Measured: 30 days from start of treatment
Progression Free Survival (PFS)
Incidence of progression free survival.
Measured: 6 months from start of treatment
Overall Survival (OS)
Incidence of overall survival.
Measured: 6 months from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Aug 201825 Jan 2022

First posted31 Jan 2018
Study start13 Aug 2018
Primary completion25 Jan 2022
Study completion25 Jan 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03417154
Sponsor's protocol ID: 2017LS116
Other IDs: HM2017-33
Status last verified: May 2023
First submitted: 2 Jan 2018
Last updated: 26 May 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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