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

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00274846
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arm: 1
• Duration (Months): 39
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: aldesleukin; Biological: therapeutic allogeneic lymphocytes; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: in vitro treated peripheral blood stem cell transplantation	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Allogeneic Natural Killer Cells in Patients With Relapsed Acute Myelogenous Leukemia
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Jun 1, 2008
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00274846
• Other Study ID Numbers: CDR0000450852; UMN-2004LS073; UMN-MT2004-25
• First Posted: Jan 11, 2006
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: 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)
• Additional relevant MeSH terms: Leukemia; Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate

Study Results

Participant Flow

Arm/Group Title	Patients With Relapsed/Refractory Acute Myeloid Leukemia
Arm/Group Description	Patients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled.
Period Title: Overall Study
STARTED	21
COMPLETED	20
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Patients With Relapsed/Refractory Acute Myeloid Leukemia
Arm/Group Description	Patients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled.
Overall Participants	21
Age (Count of Participants)
<=18 years	3 14.3%
Between 18 and 65 years	17 81%
>=65 years	1 4.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (18.8)
Sex: Female, Male (Count of Participants)
Female	10 47.6%
Male	11 52.4%
Region of Enrollment (participants) [Number]
United States	21 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Relapsed/Refractory AML - Evaluable Group
Arm/Group Description	Patients who are evaluable; received adequate (dose of 1.5-8 x 10^7/kg natural killer (NK) cells 14 days after treatment with chemotherapy and allogeneic NK cell-enriched immune therapy.
Measure Participants	20
Number [Participants]	2 9.5%

2. Secondary Outcome

Title	Number of Patients With Complete Remission
Description	Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (< 1% blasts in bone marrow with neutrophil recovery).
Time Frame	Day 28-35

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With Relapsed/Refractory AML - Evaluable Group
Arm/Group Description	Patients who are evaluable; received adequate (dose of 1.5-8 x 10^7/kg natural killer (NK) cells 14 days after treatment with chemotherapy and allogeneic NK cell-enriched immune therapy.
Measure Participants	20
Number [Participant]	2

3. Secondary Outcome

Title	Median Time to Disease Relapse (Months)
Description	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.
Time Frame	From 1st Day of treatment until death or receipt of bone marrow transplant.

Outcome Measure Data

Analysis Population Description

Only 2 of 20 patients that received adequate Natural Killer Cells achieved complete remission, and were therefore evaluable for the time to relapse endpoint.

Arm/Group Title	Patients Achieving Complete Remission - Responders
Arm/Group Description	Patients who achieved complete remission (CR) as judged by morphological criteria; only these patients can be judged for time to relapse.
Measure Participants	2
Median (Full Range) [Months]	7.3

4. Secondary Outcome

Title	Overall Survival Time of Patients With Complete Remission
Description	Median number of months patients were alive after NK cell infusion.
Time Frame	From Day 1 of Treatment until death or patient received bone marrow transplant.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients Achieving Complete Remission - Responders
Arm/Group Description	Patients who achieved complete remission (CR) as judged by morphological criteria; only these patients can be judged for time to relapse.
Measure Participants	2
Median (Full Range) [Months]	13

5. Secondary Outcome

Title	Number of Patients With Complete Remission and Natural Killer Cell Expansion
Description	Includes patients who had both a complete remission of disease and an expansion of natural killer cells.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

Unable to evaluate due to low complete remission rate.

Arm/Group Title	Patients With Relapsed/Refractory AML - Evaluable Group
Arm/Group Description	Patients who are evaluable; received adequate (dose of 1.5-8 x 10^7/kg natural killer (NK) cells 14 days after treatment with chemotherapy and allogeneic NK cell-enriched immune therapy.
Measure Participants	0

Adverse Events

Time Frame	Events were monitored from Day 1 of study through Day 60 post-natural killer cell infusion.
Adverse Event Reporting Description	All "other" adverse events that occurred were expected and not captured.
Arm/Group Title	Patients With Relapsed/Refractory Acute Myeloid Leukemia
Arm/Group Description	Patients who met study criteria - relapsed or refractory acute myelogenous leukemia - and were enrolled.
All Cause Mortality
	Patients With Relapsed/Refractory Acute Myeloid Leukemia
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients With Relapsed/Refractory Acute Myeloid Leukemia
	Affected / at Risk (%)	# Events
Total	19/21 (90.5%)
Blood and lymphatic system disorders
Hemorrhage, CNS	1/21 (4.8%)	1
Hemorrhage, lung	1/21 (4.8%)	1
General disorders
Death due to progressive disease	14/21 (66.7%)	14
Infections and infestations
Infection	4/21 (19%)	4
Nervous system disorders
Leukoencephalopathy	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Patients With Relapsed/Refractory Acute Myeloid Leukemia
	Affected / at Risk (%)	# Events
Total	0/21 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.