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Alloreactive NK Cells for Allogeneic Stem Cell Transplantation for AML and MDS
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, July 2009
First Received: November 20, 2006   Last Updated: July 28, 2009   History of Changes
Sponsor: M.D. Anderson Cancer Center
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00402558
  Purpose

The primary objectives are the following:

  • To assess the safety of infusing alloreactive NK cells from a haploidentical relative and to determine the maximum tolerated dose of these cells given in combination with busulfan, fludarabine, Thymoglobulin and allogeneic transplantation from a separate HLA identical donor for treatment of AML/MDS.
  • To determine the rate of engraftment, graft-vs-host disease (GVHD), immune reconstitution and survival after infusion of alloreactive haploidentical NK cells effects.

Condition Intervention Phase
Myelodysplastic Syndrome
Leukemia
Drug: Thymoglobulin
Drug: Busulfan
Drug: Fludarabine
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Alloreactive NK Cells With Busulfan, Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplantation for AML and MDS

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose of NK cells [ Time Frame: Continual Reassessment (Baseline, 3, 6 and 12 Months Follow Ups) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 18
Study Start Date: May 2006
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Thymoglobulin + Busulfan + Fludarabine: Experimental Drug: Thymoglobulin
1.5 mg/kg By Vein Daily x 3 Days
Drug: Busulfan
130 mg/m^2 By Vein Over 3 Hours x 4 Days
Drug: Fludarabine
40 mg/m^2 By Vein Over 30 Minutes x 4 Days

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with age </= 70 years with one of of the following: Acute myeloid leukemia past first remission, in first or subsequent relapse, in second or greater remission or primary induction failure; Myelodysplastic syndromes with intermediate or high risk IPSS score; CML which has progressed to accelerated phase or blast crisis despite imatinib treatment
  2. Patients must have an HLA matched related or unrelated donor willing to donate for allogeneic peripheral blood progenitor cell transplantation.
  3. Patients must have a haploidentical relative who is predicted to be alloreactive based upon the presence of the relevant KIR genes and incompatibility with the recipient for HLA C and Bw antigens.
  4. Zubrod performance status </= 2.
  5. Left ventricular ejection fraction >/= 45%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
  6. No symptomatic pulmonary disease. FEV1, FVC and DLCO >/= 50% of expected, corrected for hemoglobin.
  7. Serum creatinine </= 1.8mg%.
  8. SGPT </= 200 IU/ml unless related to patients malignancy.
  9. Bilirubin </= 1.5 mg/dl (unless Gilbert's syndrome).No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
  10. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
  11. No known allergy to mouse proteins or monoclonal antibodies

Exclusion Criteria:

  1. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol PI is the final arbiter of eligibility.
  2. Pleural/pericardial effusion or ascites estimated to be >1L.
  3. HIV-positive.
  4. Pregnancy: Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
  5. Known allergy to mouse proteins.
  6. Patient has received other systemic chemotherapeutic drugs (including Mylotarg) within 21 days prior to trial enrollment. (Hydroxyurea or low dose ara-c < 20 mg/m2/d is permitted if indicated to control induction refractory disease, and IT chemotherapy is allowed if indicated as maintenance treatment for previously diagnosed LMD, that has been in remission for at least 3 months prior to enrollment on this study).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00402558

Contacts
Contact: Richard E. Champlin, MD 713-792-8750

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Richard E. Champlin, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Richard E. Champlin, MD U.T.M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: U.T.M.D. Anderson Cancer Center ( Richard E. Champlin, MD/Professor )
Study ID Numbers: 2005-0508
Study First Received: November 20, 2006
Last Updated: July 28, 2009
ClinicalTrials.gov Identifier: NCT00402558     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Acute Myeloid Leukemia
Chronic Myelogenous Leukemia
Myelodysplastic Syndrome
Leukemia
NK Cells
Natural Killer Cells
Fludarabine
Busulfan
Thymoglobulin
AML
CML
MDS
ATG
Antithymocyte globulin
Busulfex
Myleran®
Fludarabine Phosphate

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Vidarabine
Antimetabolites, Antineoplastic
Precancerous Conditions
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia
Preleukemia
Pathologic Processes
Syndrome
Therapeutic Uses
Alkylating Agents
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Neoplasms
Busulfan
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating
Bone Marrow Diseases

ClinicalTrials.gov processed this record on November 30, 2009