Personalized NK Cell Therapy in CBT
Summary
This phase II clinical trial studies how well personalized natural killer (NK) cell therapy works after chemotherapy and umbilical cord blood transplant in treating patients with myelodysplastic syndrome, leukemia, lymphoma or multiple myeloma. This clinical trial will test cord blood (CB) selection for human leukocyte antigen (HLA)-C1/x recipients based on HLA-killer-cell immunoglobulin-like receptor (KIR) typing, and adoptive therapy with CB-derived NK cells for HLA-C2/C2 patients. Natural killer cells may kill tumor cells that remain in the body after chemotherapy treatment and lessen the risk of graft versus host disease after cord blood transplant.
Detailed description
PRIMARY OBJECTIVES: I. Progression-free survival (PFS) time. SECONDARY OBJECTIVES: I. Overall survival (OS) time. II. Transplant related mortality (TRM). III. Graft versus host disease (GVHD). IV. Infection OUTLINE: Patients are assigned to 1 of 3 preparative regimens. MYELOABLATIVE REGIMEN 1: Patients receive anti-thymocyte globulin intravenously (IV) over 4 hours on days -9 and -8, fludarabine phosphate IV over 1 hour, clofarabine IV over 1 hour, and busulfan IV over 3 hours on days -7 to -4. Patients undergo total body irradiation (TBI) on day -3. NON-MYELOABLATIVE REGIMEN 2: Patients with cluster of differentiation (CD)20 positive malignancies receive rituximab IV over 6 hours on day -9. Patients receive anti-thymocyte globulin IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 1 hour on days -6 to -3, and cyclophosphamide IV over 3 hours on day -6 and undergo TBI on day -1 at the discretion of the investigator(s). REDUCED INTENSITY REGIMEN 3: Patients receive anti-thymocyte globulin IV over 4 hours on days -7 and -6, fludarabine phosphate IV over 1 hour on days -5 to -2, and melphalan IV over 30 minutes on day -2. UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo umbilical cord blood transplantation on day 0. NK CELLS INFUSION: Patients receive NK cells IV over 30 minutes between days 30-180. After completion of study treatment, patients are followed up at 1, 7, 14, 28, 45, 60, and 100 days, and at 6, 9, and 12 months, and then yearly for up to 4 years.
Arms & interventions
- BiologicalAllogeneic Natural Killer Cell Line NK-92
Given IV
- BiologicalAnti-Thymocyte Globulin
Given IV
- DrugBusulfan
Given IV
- DrugClofarabine
Given IV
- DrugCyclophosphamide
Given IV
- DrugFludarabine Phosphate
Given IV
- OtherLaboratory Biomarker Analysis
Correlative studies
- DrugMelphalan
Given IV
- BiologicalRituximab
Given IV
- RadiationTotal-Body Irradiation
Undergo total body irradiation
- ProcedureUmbilical Cord Blood Transplantation
Undergo umbilical cord blood transplantation
Outcome measures
Primary
Progression free survival (PFS) time in C2C2 patients
Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, human leukocyte antigen (HLA) match, cytomegalovirus (CMV) status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.
Time frame: From the date of engraftment to disease progression or death, assessed up to 4 years
Progression free survival (PFS) time in C1 patients
Distributions of time-to-event variables will be estimated using the method of Kaplan and Meier, and Bayesian regression models will be used to assess the relationship of each outcome with patient covariates, including disease stage, KIR haplotype, age, diagnosis, HLA match, CMV status, and gender. Categorical outcomes will be evaluated by tabulation and Bayesian regression modeling.
Time frame: From the date of cord blood transplant to disease progression or death, assessed up to 4 years
Secondary
Overall survival time
Time frame: Up to 4 years
Incidence of transplant related mortality
Time frame: Up to 4 years
Incidence of graft-versus host disease
Time frame: Up to 4 years
Incidence of infection
Time frame: Up to 4 years
Eligibility criteria
Study locations (1)
M D Anderson Cancer Center
Houston, Texas, 77030