Donor Peripheral Stem Cell Transplant in Treating Patients With Relapsed Acute Myeloid Leukemia

Phase 2

Completed

• Conditions: Leukemia
• Interventions: Biological: aldesleukin; Biological: therapeutic allogeneic lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: in vitro treated peripheral blood stem cell transplantation

• Registration Number: NCT00274846
• Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary

RATIONALE: Giving chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer (NK) cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This clinical trial is studying how well a peripheral stem cell transplant using NK cells from a donor works in treating patients with relapsed acute myeloid leukemia.

Detailed Description

OBJECTIVES:

Primary

* Evaluate the in vivo expansion of natural killer (NK) cells 14 days after treatment with allogeneic NK cell-enriched peripheral blood stem cell transplantation in patients with relapsed acute myeloid leukemia.

Secondary

* Determine the response rate, in terms of complete remission, in patients treated with this regimen.

* Correlate complete remission rate with NK cell expansion, interleukin-15 levels, and donor/recipient killer immunoglobulin receptor (KIR) ligand matching status in patients treated with this regimen.

* Determine the overall and progression-free survival of patients treated with this regimen.

* Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label study.

* Induction therapy: Patients receive fludarabine IV on days -6 to -2 and cyclophosphamide IV on day -5 or on days -5 and -4.

* Allogeneic natural killer (NK) cell-enriched peripheral blood stem cell transplantation: Patients receive allogeneic NK cell-enriched peripheral blood stem cells IV over 15-60 minutes on day 0. Patients also receive interleukin-2 subcutaneously beginning on day 0 and continuing 3 times a week for up to 2 weeks.

After completion of study treatment, patients are followed periodically for 3 months.

Study Timeline

• Study Start: 2005-03
• Study First Submitted: 2006-01-10
• Study First Submitted QC: 2006-01-10
• Study First Posted: 2006-01-11
• Primary Completion: 2008-06
• Study Completion: 2008-06
• Results First Submitted: 2009-07-24
• Results First Submitted QC: 2009-07-31
• Results First Posted: 2009-09-07
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-03
• Last Update Posted: 2017-12-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria:

  • Primary refractory disease (no complete response [CR] after ≥ 2 induction therapies)
  • Relapsed disease not in CR after ≥ 1 course of standard reinduction therapy
  • Secondary AML from myelodysplastic syndromes
  • Disease relapsed ≥ 2 months after transplant and no option of donor lymphocyte infusions (e.g., recipients of autologous or umbilical cord blood transplants)
  • Chronic myelogenous leukemia with myeloid blast crisis not in second chronic phase after at least one cycle of standard chemotherapy and imatinib
  • Over 60 years of age with relapse within 6 months after completion of last chemotherapy
  • Over 60 years of age with blast count < 30% within 10 days before study entry

• Related HLA-haploidentical natural killer cell donor available

• No severe organ damage (by clinical or laboratory assessment)

• Performance status 50-100%

• No evidence of active infection on chest X-ray

• No active fungal infection

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Exclusion Criteria

• Active central nervous system (CNS) leukemia
• Pleural effusions large enough to be detectable by chest x-ray
• Pregnant or nursing (positive pregnancy test)
• Fertile patients must use effective contraception
• Less than 60 days since prior transplant
• Less than 3 days since prior prednisone
• Less than 3 days since other prior immunosuppressive medication

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intent-to-Treat	aldesleukin	All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10\^7/kg.)
Intent-to-Treat	therapeutic allogeneic lymphocytes	All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10\^7/kg.)
Intent-to-Treat	in vitro treated peripheral blood stem cell transplantation	All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10\^7/kg.)
Intent-to-Treat	cyclophosphamide	All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10\^7/kg.)
Intent-to-Treat	fludarabine phosphate	All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10\^7/kg.)

Primary Outcome Measures

Name	Time	Method
Number of Patients With Natural Killer (NK) Cell Expansion	Study Day 14	Evaluation of expansion of donor allogeneic natural killer (NK) cells at day 14 following infusion (\>100 donor-derived NK cells per uL of patient blood detectable at day +14).

Secondary Outcome Measures

Name	Time	Method
Overall Survival Time of Patients With Complete Remission	From Day 1 of Treatment until death or patient received bone marrow transplant.	Median number of months patients were alive after NK cell infusion.
Number of Patients With Complete Remission and Natural Killer Cell Expansion	Day 14	Includes patients who had both a complete remission of disease and an expansion of natural killer cells.
Number of Patients With Complete Remission	Day 28-35	Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (\< 1% blasts in bone marrow with neutrophil recovery).
Median Time to Disease Relapse (Months)	From 1st Day of treatment until death or receipt of bone marrow transplant.	Follow-up continued every 3 months after the allogeneic natural killer (NK) cell infusion, unless they were transplanted, relapsed or had progressive disease. Time in months to relapse of disease is calculcated from 1st day of treatment with NK cells. Relapse occurs when leukemia is detected in bone marrow or blood.

Trial Locations

Locations (1)

Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States