Alloreactive NK Cells for Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Alloreactive NK Cells With Busulfan, Fludarabine and Thymoglobulin for Allogeneic Stem Cell Transplantation for AML and MDS
3 other identifiers
interventional
15
1 country
1
Brief Summary
The goal of this clinical research study is to determine the safety and effects of giving a special kind of immune cells called "alloreactive natural killer (NK) cells" with high dose chemotherapy and allogeneic hematopoeitic stem cell transplantation with the goal of defining the maximum tolerated dose of NK cells. The NK cells will be donated from a relative of yours who has certain genetic type in their blood called HLA, that almost matches yours. The stem cells you will receive will come from a separate HLA matched (HLA A, B, C, DR) relative or unrelated donor. The safety of this treatment will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2006
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
May 1, 2006
CompletedFirst Submitted
Initial submission to the registry
November 20, 2006
CompletedFirst Posted
Study publicly available on registry
November 22, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2014
CompletedMay 8, 2015
May 1, 2015
7.9 years
November 20, 2006
May 6, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose of NK cells
Continual Reassessment (Baseline, 3, 6 and 12 Months Follow Ups)
Study Arms (1)
Thymoglobulin + Busulfan + Fludarabine
EXPERIMENTALThymoglobulin 1.5 mg/kg by vein for 3 days. Busulfan 130 mg/m\^2 by vein for 4 days. Fludarabine 40 mg/m\^2 by vein for 4 days. Alloreactive NK infusion from haploidentical donor on Day -8. Alloreactive NK cell infusion given at one of 4 dose levels 10e6, 5 x 10e6, 3 x 10e7 cells/kg and 3 x10e7 NK Cells plus systemic interleukin-2 treatment. The 4th dose level is 3 x 107 NK cells/kg plus systemic interleukin-2 at a dose of 0.5 million units per day subcutaneously starting on Day -8 (day of the NK cell infusion) to Day -4. G-CSF 5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count is \> 500 x 109/L for 3 consecutive days. Tacrolimus starting dose of 0.015 mg/kg daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus changed to oral dosing when tolerated and can be tapered off after Day +90 if no GVHD is present. Methotrexate 5 mg/m2 by vein on Days 1, 3 and 6 and Day +11 post transplant.
Interventions
1.5 mg/kg By Vein Daily x 3 Days
130 mg/m\^2 By Vein Over 3 Hours x 4 Days
40 mg/m\^2 By Vein Over 30 Minutes x 4 Days
Alloreactive NK infusion from haploidentical donor on Day -8. The alloreactive NK cell infusion given at one of 4 dose levels 10e6, 5 x 10e6, 3 x 10e7 cells/kg and 3 x10e7.
5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is \> 500 x 109/L for 3 consecutive days.
Starting dose of 0.015 mg/kg as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus changed to oral dosing when tolerated and can be tapered off after Day +90 if no GVHD is present.
5 mg/m2 intravenously on Days 1, 3 and 6 and Day +11 post transplant.
0.5 million units per day subcutaneously starting on Day -8 (day of the NK cell infusion) to Day -4 only to participants receiving fourth dose level of NK cells.
Eligibility Criteria
You may qualify if:
- 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
- Patients must have an HLA matched (HLA A, B, C, DR) related or unrelated donor willing to donate for allogeneic peripheral blood progenitor cell transplantation. (Recent large analyses of the National Marrow Donor Program indicate that a mis-match at the DQ locus has no adverse effect on outcome. The current national standard of care is to consider only these 4 loci in identifying suitably "matched" donors.)
- 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.
- Zubrod performance status \</= 2.
- Left ventricular ejection fraction \>/= 45%. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
- No symptomatic pulmonary disease. forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) \>/= 50% of expected, corrected for hemoglobin.
- Serum creatinine \</= 1.8mg%.
- Serum glutamate pyruvate transaminase (SGPT) \</= 200 IU/ml unless related to patients malignancy.
- 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.
- Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
- No known allergy to mouse proteins or monoclonal antibodies
You may not qualify if:
- Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy. The Protocol PI is the final arbiter of eligibility.
- Pleural/pericardial effusion or ascites estimated to be \>1L.
- HIV-positive.
- Pregnancy: Positive Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
- Known allergy to mouse proteins.
- Patient has received other systemic chemotherapeutic drugs (including Mylotarg) within 14 days prior to trial enrollment or has unresolved grade \>1 toxicity from prior chemotherapy treatment. (Hydroxyurea or low dose ara-c less than or equal to 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 lumbar microdiscectomy (LMD), that is in remission prior to enrollment on this study).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
UT MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Richard E. Champlin, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 20, 2006
First Posted
November 22, 2006
Study Start
May 1, 2006
Primary Completion
April 1, 2014
Study Completion
April 1, 2014
Last Updated
May 8, 2015
Record last verified: 2015-05