Clinical trial NCT00274846: Donor Peripheral Stem Cell Transplant in Treating Patients With Relapsed Acute Myeloid Leukemia
Official title: Allogeneic Natural Killer Cells in Patients With Relapsed Acute Myelogenous Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: 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)
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2006-01-11
Enrollment: 21
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients With Natural Killer (NK) Cell Expansion
timeFrame: Study Day 14
Secondary outcomes:
measure: Number of Patients With Complete Remission
timeFrame: Day 28-35
measure: Median Time to Disease Relapse (Months)
timeFrame: From 1st Day of treatment until death or receipt of bone marrow transplant.
measure: Overall Survival Time of Patients With Complete Remission
timeFrame: From Day 1 of Treatment until death or patient received bone marrow transplant.
measure: Number of Patients With Complete Remission and Natural Killer Cell Expansion
timeFrame: Day 14
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Jeffrey Miller, MD
role: STUDY_CHAIR
References:
citation: 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.