Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant
Reduced Intensity Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) Supplemented With Donor Natural Killer (NK) Cell Infusions in Patients With High Risk Myeloid Malignancies Who Are Unsuitable for Fully Myeloablative Transplantation
3 other identifiers
interventional
50
1 country
1
Brief Summary
RATIONALE: Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total body irradiation, before peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also 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. Giving IL-2 (aldesleukin) after NK cell infusion may stimulate them to kill any remaining cancer cells. PURPOSE: This phase I/II (currently enrolling in phase II) trial is studying how well a donor natural killer cell infusion works in treating patients who are undergoing donor stem cell transplant for acute myeloid leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2005
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2005
CompletedFirst Submitted
Initial submission to the registry
March 15, 2006
CompletedFirst Posted
Study publicly available on registry
March 17, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2011
CompletedResults Posted
Study results publicly available
July 3, 2015
CompletedDecember 28, 2017
December 1, 2017
6.2 years
March 15, 2006
June 11, 2015
December 3, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Disease-free Survival at 6 Months
Number of patients alive without evidence of disease at 6 months after transplant
Month 6
Disease-free Survival at 1 Year
Number of patients alive without evidence of disease at 1 year after transplant
1 Year
Secondary Outcomes (7)
In Vivo Expansion of a Donor NK Cells NK Cell Product
12 - 14 days after NK cell infusion
Number of Patients With Graft Failure
Day 28
Incidence of Grade III-IV Acute Graft Versus Host Disease
Month 6
Number of Patients With Treatment-Related Mortality
Day 100
Incidence of Chronic Graft Versus Host Disease
1 Year
- +2 more secondary outcomes
Study Arms (2)
SCT w/Donor Natural Killer Cells - short schema
EXPERIMENTALPatients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
SCT w/Donor Natural Killer Cells - extended schema
EXPERIMENTALPatients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Interventions
Administered subcutaneously (SQ) 9 million units every other day beginning Day -12 through -2 (evening of natural killer cell infusion) for a total of 6 doses.
Infusion given on Day -12; The targeted infused cell dose of CD3- CD19- selected NK product is within the range of 2-3 x 10\^7 cells/kg.
Administered intravenously (IV) 50 mg/kg on Day -15
Administered intravenously (IV) 40 mg/m\^2 on Days -18 through -14
On day 0, patients will receive an allogeneic transplant using pool cells from the day -1 and day 0 PBSC which will be CD34+ selected as the donor graft. The graft will be infused over 15-60 minutes.
Administered on Day -13, 200 cGy two times.
intravenous (IV) 3 mg/kg on Day 0 (day of donor CD34 cell infusion)
1.5 mg/kg by mouth or intravenously for target dose range of 150-250; day -15 through day -8.
Eligibility Criteria
You may qualify if:
- High risk acute myeloid leukemia (AML) fitting within one of the following disease groups:
- Primary induction failure defined as no complete remission (CR) after two or more induction cycles. For primary induction failure (PIF) or refractory AML, the patient must have \<5% circulating blasts (and \<1000 absolute circulating blasts) beyond Day 28 after last chemo. During work-up period if circulating blasts rise above these levels, the patient is ineligible. The use of hydrea or other non-induction cytotoxic agents is not allowed to reduce blasts and achieve this eligibility. If the blasts are higher than these limits, the patient should be treated on an alternative therapeutic protocol or receive another reinduction attempt. (See section 7 regarding final check of blast status within 7 days of preparative regimen start).
- Relapsed AML with low disease burden must have less than 5% marrow blasts at time of enrollment for patients who did not receive re-induction or measured at least 28 days from the start of reinduction therapy for patients who did receive re-induction (maximum of 2 re-induction attempts). Patients who have relapsed more than 12 months following a prior HCT and did not reach CR following one re-induction cycle but have less than 10% marrow blasts are eligible.
- CR3 or greater. This will include CRp defined as CR without platelet recovery to 100,000/mcL.
- CR1 or CR2 with high risk features (therapy induced, prior myelodysplastic syndrome \[MDS\] or myeloproliferative disease \[MPD\], high risk cytogenetic or molecular phenotype) with no available alternate (sibling, unrelated donor \[URD\] or umbilical cord blood \[UCB\]) donors.
- Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and CFS must be clear for at least 2 weeks prior to enrollment.
- Available related HLA-haploidentical donor (3-5 of 6 HLA, A, B and DRB1 matched)
- Karnofsky performance status \> 50
- Pulmonary Function: oxygen saturation ≥ on room air and diffusion lung capacity for carbon monoxide (DLCOcor) ≥ 40%
- Cardiac Function: Ejection fraction (EF) ≥ 30%, no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to Day 0
- Women of child bearing potential must have a negative pregnancy test within 14 days prior to study registration and agree to use adequate birth control during study treatment
- Human anti-mouse antibody (HAMA) monitoring: All subjects will be questioned about prior exposure to antibody therapy (including OKT3, rituximab, trastuzumab, etc).
- For subjects with no prior antibody therapy exposure, no further action will be taken
- For subjects who have received previous antibody therapies 10 ml of serum will be drawn before starting therapy. The presence of HAMA will not preclude proceeding with treatment.
- +1 more criteria
You may not qualify if:
- Biphenotypic leukemia
- New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (CT) scan that has not been evaluated with bronchoscopy, if feasible. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (2 weeks for presumed or documented fungal infections). Surgical resection waives any waiting requirements.
- Uncontrolled bacterial or viral infections. Chronic asymptomatic viral hepatitis is allowed.
- Known hypersensitivity to any of the study agents used
- Received other investigational drugs within the 14 days before enrollment
- Donor Selection:
- years of age
- \> 40 kilogram body weight
- In general good health as determined by the evaluating physician
- Donors must be HLA-A, B, DRB1 haploidentical (3-5/6 antigens HLA, A, B, DRB1) match to recipient. Patients and donors will be typed for HLA-A, B and C using at least intermediate resolution DNA techniques for DRB1 at high (allele) resolution. KIR B genotyping will be done on all haploidentical donors, and when feasible, the donor with the most favorable KIR gene profile will be used.
- Able and willing to have up to 4 separate apheresis collections per formed
- Not pregnant
- Human immunodeficiency virus (HIV): HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative
- Voluntary written consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Sarah Cooley, M.D.
- Organization
- Masonic Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Sarah Cooley, MD
Masonic Cancer Center, University of Minnesota
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 15, 2006
First Posted
March 17, 2006
Study Start
January 1, 2005
Primary Completion
March 1, 2011
Study Completion
March 1, 2011
Last Updated
December 28, 2017
Results First Posted
July 3, 2015
Record last verified: 2017-12