Donor Natural Killer Cells and Donor Stem Cell Transplant in Treating Patients With High Risk Myeloid Malignancies
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|ClinicalTrials.gov Identifier: NCT01823198|
Recruitment Status : Recruiting
First Posted : April 4, 2013
Last Update Posted : May 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Acute Myeloid Leukemia in Remission Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Blasts Under 20 Percent of Bone Marrow Nucleated Cells Blasts Under 20 Percent of Peripheral Blood White Cells Chronic Myelomonocytic Leukemia High Risk Myelodysplastic Syndrome Myelodysplastic Syndrome Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Therapy-Related Acute Myeloid Leukemia Therapy-Related Myelodysplastic Syndrome||Biological: Aldesleukin Biological: Allogeneic CD56-positive CD3-negative Natural Killer Cells Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Busulfan Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Procedure: Peripheral Blood Stem Cell Transplantation Other: Pharmacological Study||Phase 1 Phase 2|
I. Assess the safety of infusing ex vivo expanded natural killer (NK) cells in patients receiving busulfan-fludarabine phosphate (fludarabine) with an allogeneic human leukocyte antigen (HLA) matched hematopoietic transplantation for myeloid malignancies. Two sources of NK cells could be studied, depending on what donor source is available: cells from the HLA matched related donor or cells from an unrelated cord blood unit.
II. For each source of NK cells: the maximum tolerated cell dose; the phenotype and function of the ex vivo expanded NK cells and their survival in vivo; the rate of engraftment, graft-vs.-host disease (GVHD), immune reconstitution, relapse rates and survival for patients receiving this regimen will be determined.
OUTLINE: This is a phase I, dose-escalation study of NK cells followed by a phase II study.
Patients receive fludarabine phosphate intravenously (IV) over 1 hour and busulfan IV over 3 hours on days -13 to -10. Patients then receive allogeneic CD56-positive CD3-negative natural killer cells IV over 1 hour on day -8. Patients also receive aldesleukin subcutaneously (SC) once daily (QD) on days -8 to -4. Patients then undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NK Cells With HLA Compatible Hematopoietic Transplantation for High Risk Myeloid Malignancies|
|Actual Study Start Date :||June 11, 2013|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||June 30, 2020|
Experimental: Treatment (NK cells, PBSC transplant)
Patients receive fludarabine phosphate IV over 1 hour and busulfan IV over 3 hours on days -13 to -10. Patients then receive allogeneic CD56-positive CD3-negative natural killer cells IV over 1 hour on day -8. Patients also receive aldesleukin SC QD on days -8 to -4. Patients then undergo allogeneic PBSC transplant on day 0.
Biological: Allogeneic CD56-positive CD3-negative Natural Killer Cells
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic PBSC transplant
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo allogeneic PBSC transplant
Other: Pharmacological Study
- Optimal natural killer cell dose based on incidence of dose-limiting toxicity [ Time Frame: Up to 42 days ]The Bayesian model averaging (BMA)-continual reassessment method (CRM) will be applied. The data will be analyzed by fitting the CRM model to the final data and summarizing the posterior distributions of the probability of overall toxicity and of each adverse event in the definition of toxicity at the maximum tolerated dose and at the other doses, by tabulating the counts and rates of all secondary events both overall and cross-tabulated with dose, and fitting appropriate logistic or ordinal outcome regression models to assess possible patterns of change with dose.
- Overall survival time [ Time Frame: Up to 5 years ]Will assess overall survival time.
- Disease-free survival time [ Time Frame: Up to 5 years ]Will assess disease-free survival time.
- Incidence of graft versus host disease [ Time Frame: Up to 5 years ]Will assess incidence of graft versus host disease.
- Incidence of grade 3 toxicities [ Time Frame: Up to 5 years ]It will be determined if any grade 3 toxicities occur in increased frequency compared to historical experience with this regime without natural killer cells.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01823198
|Contact: Richard E. Champlin, BS,MDemail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Richard E. Champlin 713-792-8750|
|Principal Investigator: Richard E. Champlin|
|Principal Investigator:||Richard E Champlin||M.D. Anderson Cancer Center|