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

Allogeneic Natural Killer Cells in Patients With Relapsed Acute Myelogenous Leukemia

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.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Biological: aldesleukin; Biological: therapeutic allogeneic lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: in vitro treated peripheral blood stem cell transplantation

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 Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intent-to-Treat; All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10^7/kg.)

Biological: aldesleukin; 10 million units three times a week for a total of 6 doses. For any subject less than 45 kilograms the IL-2 will be given at 5 million units per meter squared three times weekly for a total of 6 doses; Other Names: IL-2; Biological: therapeutic allogeneic lymphocytes; Cells infused per kg. 1.5-8.0 x 10^7/kg Total cells infused(for 70 kg. adult) 1.05 - 5.6 x 10^9; Other Names: lymphocytes; Drug: cyclophosphamide; Days -5 and -4: 60 mg/kg; Other Names: Cytoxan; Drug: fludarabine phosphate; Days -5 through -2: 25 mg/m^2; Other Names: Fludara; Procedure: in vitro treated peripheral blood stem cell transplantation; Day 0 infuse natural killer cells; Other Names: Natural Killer Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Natural Killer (NK) Cell Expansion	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).	Study Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Complete Remission	Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery).	Day 28-35
Median Time to Disease Relapse (Months)	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.	From 1st Day of treatment until death or receipt of bone marrow transplant.
Overall Survival Time of Patients With Complete Remission	Median number of months patients were alive after NK cell infusion.	From Day 1 of Treatment until death or patient received bone marrow transplant.
Number of Patients With Complete Remission and Natural Killer Cell Expansion	Includes patients who had both a complete remission of disease and an expansion of natural killer cells.	Day 14

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Study Chair: Jeffrey Miller, MD, Masonic Cancer Center, University of Minnesota

Publications and helpful links

General Publications

• Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, McGlave P, Weisdorf DJ, Blazar BR, Miller JS. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood. 2014 Jun 19;123(25):3855-63. doi: 10.1182/blood-2013-10-532531. Epub 2014 Apr 9.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (Estimate): January 11, 2006

Study Record Updates

• Last Update Posted (Actual): December 28, 2017
• Last Update Submitted That Met QC Criteria: December 3, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); secondary acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent childhood acute myeloid leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate
• Other Study ID Numbers: CDR0000450852; UMN-2004LS073 (Other Identifier: Clinical Trials Office, University of Minnesota); UMN-MT2004-25 (Other Identifier: Blood and Marrow Transplantation Program)