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

Study Overview
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Brief Summary
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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)

Official Title
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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.

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Cytarabine
* Drug: Nivolumab
* Drug: Cytarabine
* Drug: Nivolumab
* Biological: G-CSF mobilized HLA-haploidentical donor PBSC


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ara-C+HaploLymphocyte+Nivo<br>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<br>* Cytarabine 500-1000 mg/m2 bid IV infusion on D-4, -3, -2<br>* Other names: Ara-C;Drug: Nivolumab<br>* Nivolumab 40 mg IV infusion on D+5<br>* Other names: Opdivo;Biological: G-CSF mobilized HLA-haploidentical donor PBSC<br>* G-CSF mobilized HLA-haploidentical donor peripheral blood stem cells IV infusion on D0<br>|
| Experimental: Ara-C+ Nivo<br>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<br>* Cytarabine 500-1000 mg/m2 bid IV infusion on D+1, +2, +3<br>* Other names: Ara-C;Drug: Nivolumab<br>* Nivolumab 40 mg IV infusion on D+1<br>* Other names: Opdivo;|

What is the study measuring?
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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 |