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

NCT ID: NCT00274846

Last Updated: 2017-12-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2008-06-30

Brief Summary

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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

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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.

Conditions

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Leukemia

Keywords

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recurrent adult acute myeloid leukemia recurrent childhood acute myeloid leukemia secondary acute myeloid leukemia 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)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intent-to-Treat

All patients treated with natural killer (NK) cells (at a dose of 1.5-8 x 10\^7/kg.)

Group Type EXPERIMENTAL

aldesleukin

Intervention Type BIOLOGICAL

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

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

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

cyclophosphamide

Intervention Type DRUG

Days -5 and -4: 60 mg/kg

fludarabine phosphate

Intervention Type DRUG

Days -5 through -2: 25 mg/m\^2

in vitro treated peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Day 0 infuse natural killer cells

Interventions

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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

Intervention Type 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

Intervention Type BIOLOGICAL

cyclophosphamide

Days -5 and -4: 60 mg/kg

Intervention Type DRUG

fludarabine phosphate

Days -5 through -2: 25 mg/m\^2

Intervention Type DRUG

in vitro treated peripheral blood stem cell transplantation

Day 0 infuse natural killer cells

Intervention Type PROCEDURE

Other Intervention Names

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IL-2 lymphocytes Cytoxan Fludara Natural Killer Cells

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeffrey Miller, MD

Role: STUDY_CHAIR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 24719405 (View on PubMed)

Other Identifiers

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UMN-2004LS073

Identifier Type: OTHER

Identifier Source: secondary_id

UMN-MT2004-25

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000450852

Identifier Type: -

Identifier Source: org_study_id