Haploidentical Lymphocytes With Nivolumab/Ara-C as Consolidation in Elderly AML Patients

A Randomized Study of Haploidentical Lymphocytes With Nivolumab and Intermediate Dose Cytarabine Versus Nivolumab and Intermediate Dose Cytarabine as Consolidation Treatment in Older Adults With Acute Myeloid Leukemia.

A phase II trial to compare the efficacy and safety of nivolumab and intermediate dose cytarabine with or without haploidentical lymphocyte infusion. To identify the role of haploidentical lymphocytes in the treatment of acute myeloid leukemia in older adults. The patients will be stratified based on the remission number (first or second)

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Cytarabine; Drug: Nivolumab; Drug: Cytarabine; Drug: Nivolumab; Biological: G-CSF mobilized HLA-haploidentical donor PBSC

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 197089
    • Boris V Afanasyev, MD, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of acute myeloid leukemia with the confirmed first or second complete remission
• ≥ 55 years of age
• Not candidates for allogeneic stem cell transplantation as decided by the panel of hematologists at the transplant center
• Patients with a HLA-haploidentical donor who should be able to provide informed consent for peripheral blood apheresis
• No severe concurrent illness that limits life expectancy to less than 2 years

Exclusion Criteria:

• Uncontrolled bacterial or fungal infection at the time of enrollment
• Karnofsky index <70%
• Acute promyelocytic leukemia
• Other tumor requiring treatment at the time of enrollment
• Active or prior documented autoimmune disease requiring systemic treatment
• Somatic or psychiatric disorder making the patient unable to sign informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ara-C+HaploLymphocyte+Nivo; Patients treated with nivolumab, intermediate dose cytarabine and haploidentical lymphocyte infusion: [Cytarabine 500-1000 mg/m2 bid D-4, -3, -2 + G-CSF mobilized HLA-haploidentical donor peripheral blood stem cells infusion D0 + Nivolumab 40 mg D+5] х 2-3 cycles	Drug: Cytarabine; Cytarabine 500-1000 mg/m2 bid IV infusion on D-4, -3, -2; Other Names: Ara-C; Drug: Nivolumab; Nivolumab 40 mg IV infusion on D+5; Other Names: Opdivo; Drug: Cytarabine; Cytarabine 500-1000 mg/m2 bid IV infusion on D+1, +2, +3; Other Names: Ara-C; Drug: Nivolumab; Nivolumab 40 mg IV infusion on D+1; Other Names: Opdivo; Biological: G-CSF mobilized HLA-haploidentical donor PBSC; G-CSF mobilized HLA-haploidentical donor peripheral blood stem cells IV infusion on D0
EXPERIMENTAL: Ara-C+ Nivo; Patients treated with nivolumab and intermediate dose cytarabine: [Cytarabine 500-1000 mg/m2 bid D+1, +2, +3 + Nivolumab 40 mg D+1] х 2-3 cycles	Drug: Cytarabine; Cytarabine 500-1000 mg/m2 bid IV infusion on D-4, -3, -2; Other Names: Ara-C; Drug: Nivolumab; Nivolumab 40 mg IV infusion on D+5; Other Names: Opdivo; Drug: Cytarabine; Cytarabine 500-1000 mg/m2 bid IV infusion on D+1, +2, +3; Other Names: Ara-C; Drug: Nivolumab; Nivolumab 40 mg IV infusion on D+1; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	DFS will be assessed with Kaplan-Meier method from the date of last remission before randomization until the date of relapse or the date of death	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS will be assessed with Kaplan-Meier method from the date of last remission before randomization until the date of death from any cause	2 years
Incidence of graft-versus-host disease	Incidence of acute GVHD, grades I-IV	up to 12 months
Treatment-related adverse events as assessed by CTCAE v4.03	Toxicity parameters based on NCI CTCAE 4.03 grades: hematological toxicity (CBC), hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), fatigue (attending physician assessment), rash (attending physician assessment), colitis (attending physician assessment), pneumonitis (attending physician assessment), autoimmune disorders (level of hormones, presence of autoimmune antibodies, attending physician assessment).	up to 12 months

Collaborators and Investigators

• Sponsor: St. Petersburg State Pavlov Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 30, 2017
• Primary Completion (ACTUAL): September 30, 2018
• Study Completion (ACTUAL): September 30, 2018

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 18, 2017
• First Posted (ACTUAL): December 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Cytarabine
• Other Study ID Numbers: 31/17-n

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No