This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Giving chemotherapy with or without total body irradiation before a donor umbilical cord blood 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 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.
PRIMARY OBJECTIVES: I. To evaluate the feasibility and safety of ex-vivo expanded cord blood (CB) natural killer (NK) cells with double CB transplantation in patients with hematological malignancies. SECONDARY OBJECTIVES: I. To monitor engraftment, chimerism, graft versus host disease, and immune reconstitution in patients receiving expanded CB NK cell therapy. II. To estimate the time to platelet recovery and the time to absolute neutrophil count (ANC) recovery. III. To estimate overall survival and disease free survival at one year. IV. To study the in-vivo persistence of cord blood NK cells. OUTLINE: PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 treatment plans: TREATMENT PLAN 1: Patients receive high-dose lenalidomide orally (PO) once daily (QD) on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab intravenously (IV) over 6 hours on days -8 to -4. TREATMENT PLAN 2: Patients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo total body irradiation (TBI) on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1. NK CELL INFUSION: All patients receive ex-vivo expanded cord blood NK cells IV over 30 minutes on day -2. TRANSPLANT: All patients undergo allogeneic umbilical cord blood transplant on day 0. GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: All patients receive tacrolimus IV or PO on days -2 to 180 followed by taper and mycophenolate mofetil IV over 2 hours or PO thrice daily (TID) on days -3 to 100. After completion of study treatment, patients are followed up at 3, 6, and 12 months.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Undergo allogeneic umbilical cord blood transplant
Given IV
Given IV
Correlative studies
Given PO
Given IV
Given IV or PO
Given IV
Given IV
Given IV or PO
Undergo TBI
Undergo allogeneic umbilical cord blood transplant
M D Anderson Cancer Center
Houston, Texas, United States
Generation of a minimum of 5 x 10^6 natural killer/kg cells in at least 60% of patients (success rate)
Will be estimated with 90% credible interval.
Time frame: Up to 1 year
Treatment-related mortality
The method described by Thall, et al will be used. Will be estimated with 90% credible interval. The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Time frame: 100 days
Incidence of adverse events graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Changes from baseline in vital signs and laboratory values will be summarized. Tabulate adverse events by severity and relationship to therapy.
Time frame: Up to 1 year
Proportion of patients with acute graft-versus-host-disease
Time frame: Up to 1 year
Proportion of patients with chronic graft-versus-host-disease
Time frame: Up to 1 year
Overall survival
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Time frame: 1 year
Disease-free survival
The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Time frame: 1 year
Time to initial platelet recovery
Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.
Time frame: From the infusion of peripheral blood stem cells to the first of 3 consecutive platelet count measurements tested on different days with a count greater than or equal to 20 x 10e9/L, assessed up to 1 year
Time to initial absolute neutrophil count recovery
Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.
Time frame: From the infusion of peripheral blood stem cells to the first of 3 consecutive days of an absolute neutrophil count greater than or equal to 0.5 x 10e9/L, assessed up to 1 year
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