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| Sponsor: | Masonic Cancer Center, University of Minnesota |
|---|---|
| Information provided by: | Masonic Cancer Center, University of Minnesota |
| ClinicalTrials.gov Identifier: | NCT00303667 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Myelogenous Leukemia |
Biological: aldesleukin Biological: natural killer cells Drug: cyclophosphamide Drug: fludarabine phosphate Procedure: allogeneic hematopoietic stem cell transplantation Radiation: total body irradiation Biological: Thymoglobulin Drug: Cyclosporin A |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
| Estimated Enrollment: | 90 |
| Study Start Date: | January 2005 |
| Estimated Study Completion Date: | January 2015 |
| Estimated Primary Completion Date: | January 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Stem Cell Transplant with Donor Natural Killer Cells
Patients with high risk myeloid malignancies undergoing hematopoeitic stem cell transplant receiving donor natural killer cells.
|
Biological: aldesleukin
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.
Other Names:
Biological: natural killer cells
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.
Other Name: therapeutic allogeneic lymphocytes
Drug: cyclophosphamide
Administered intravenously (IV) 50 mg/kg on Days -16 and -15
Other Name: Cytoxan
Drug: fludarabine phosphate
Administered intravenously (IV) 35 mg/m^2 on Days -18 through -14
Other Name: Fludara
Procedure: allogeneic hematopoietic stem cell transplantation
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.
Other Name: PBSC
Radiation: total body irradiation
Administered on Day -13, 200 cGy two times.
Biological: Thymoglobulin
intravenous (IV) 3 mg/kg on Day 0 (day of donor CD34 cell infusion)
Other Name: rabbit ATG
Drug: Cyclosporin A
1.5 mg/kg by mouth or intravenously for target dose range of 150-250; day -15 through day -8.
Other Name: CSA
|
OBJECTIVES:
Primary
Secondary
Correlative
OUTLINE: This is an open-label study.
Patients receive fludarabine intravenous (IV) over 1 hour on days -18 to -14 and cyclophosphamide IV over 2 hours on days -16 and -15. Patients receive cyclosporin A on Day -15 through Day -8. Patients undergo total body irradiation on day -13. Patients then receive an infusion of donor natural killer cells on day -12 and interleukin-2 subcutaneously on alternating days between days -12 to -2. Patients receive thymoglobulin (ATG) and undergo allogeneic peripheral blood stem cell transplantation on day 0.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
4.2 High risk acute myeloid leukemia (AML) fitting within one of the following disease groups:
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.
Human anti-mouse antibody (HAMA) monitoring: All subjects will be questioned about prior exposure to antibody therapy (including OKT3, rituximab, trastuzumab, etc).
Exclusion Criteria:
Donor Selection:
Contacts and Locations| United States, Minnesota | |
| Masonic Cancer Center, University of Minnesota | |
| Minneapolis, Minnesota, United States, 55455 | |
| Principal Investigator: | Sarah Cooley, MD | Masonic Cancer Center, University of Minnesota |
More Information
| Responsible Party: | Sarah Cooley, MD, Masonic Cancer Center, University of Minnesota |
| ClinicalTrials.gov Identifier: | NCT00303667 History of Changes |
| Other Study ID Numbers: | 2004LS042, UMN-MT2003-23, UMN-IRB-0405M60481 |
| Study First Received: | March 15, 2006 |
| Last Updated: | September 27, 2011 |
| Health Authority: | United States: Food and Drug Administration |
|
NK cells natural killer cells immunotherapy hematopoietic cell transplant acute myelogenous leukemia |
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Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Cyclophosphamide Cyclosporins Cyclosporine Fludarabine monophosphate Fludarabine Aldesleukin Interleukin-2 Vidarabine Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Enzyme Inhibitors Antifungal Agents Anti-Infective Agents Dermatologic Agents Analgesics, Non-Narcotic Analgesics |