Natural Killer (NK) Cells With HLA Compatible Hematopoietic Transplantation for High Risk Myeloid Malignancies
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|ClinicalTrials.gov Identifier: NCT01823198|
Recruitment Status : Recruiting
First Posted : April 4, 2013
Last Update Posted : September 18, 2018
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant.
The goal of this clinical research study is to find the highest tolerable dose of immune cells called natural killer (NK) cells that can be given with chemotherapy and a stem cell transplant to patients with AML and MDS. Researchers want to learn if adding NK cells will help make the stem cell transplant more effective in treating the disease. The safety of this treatment will also be studied.
NK cells may kill cancer cells that remain in your body after your last chemotherapy treatment. The NK cells will be separated from blood from a relative of yours or from umbilical cord blood. These separated NK cells will then be grown in the lab to increase the number of NK cells that can be given to you by vein.
The chemotherapy given on this study will consist of the following drugs:
- Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplants.
- Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.
- IL-2 (interleukin-2) is a naturally occurring protein (cytokine) that can enhance NK cell function.
This is an investigational study. Busulfan, fludarabine, and IL-2 are FDA approved and commercially available for the treatment of other types of cancer. Their use for the treatment of AML and MDS is investigational. The use of NK cells is investigational. The NK cell process is not FDA approved or commercially available. It is currently being used for research purposes only.
Up to 72 patients will take part in this study. All will be enrolled at MD Anderson.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Drug: Busulfan Drug: Fludarabine Procedure: Alloreactive NK infusion Drug: Interleukin-2 Procedure: Stem Cell Infusion Drug: G-CSF Drug: Tacrolimus Drug: Methotrexate||Phase 1 Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Natural Killer (NK) Cells With HLA Compatible Hematopoietic Transplantation for High Risk Myeloid Malignancies|
|Actual Study Start Date :||June 2013|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2021|
Experimental: + Chemotherapy + NK Cell infusion + Stem Cell Transplant
Busulfan "test dose" of 32 mg/m2 within 2 weeks of the preparative regimen. Fludarabine 40 mg/m2 by vein on Day -13 to Day -10. Busulfan adjusted dose determined to achieve systemic exposure represented by an average daily AUC of 6000 µMol-min ± 5% for the entire 4-day treatment period on Day -13 to Day -10. Patients over age 60 and/or with performance status =2 receive and AUC of 4000 microM x min for each dose. Alloreactive NK infusion on Day -8. Alloreactive NK cell infusion given at one of 4 dose levels based on the number of NK cells (CD3-,CD 56+ cells)/kg recipient body weight. Dose levels are: 10^6, 10^7, 3 x 10^7, 10^8. Interleukin-2 0.5 million units subcutaneously on Day -8 to Day -4. Hematopoietic stem cell infusion on Day 0.
32 mg/m2 test dose based on actual body weight given by vein within 2 weeks of the preparative regimen.
Busulfan adjusted dose determined to achieve a systemic exposure represented by an average daily AUC of 6000 µMol-min ± 5% on Day -13 to Day -10. Patients over age 60 and/or with performance status =2 receive and AUC of 4000 microM x min for each dose. If it is not feasible to perform the pharmacokinetic studies, Busulfan dose of 130 mg/m2 administered (100 mg/m2 for age over 60 or PS=2).
PK-guided daily high-dose Busulfan dose(s) started immediately upon completion of the daily fludarabine doses.
40 mg/m2 by vein dosed per actual body weight/actual body surface area on Day -13 to Day -10.
Procedure: Alloreactive NK infusion
Alloreactive NK cell infusion given by vein on Day -8 at one of 4 dose levels based on the number of NK cells (CD3-,CD 56+ cells)/kg recipient body weight. Dose levels are: 10^6, 10^7, 3 x 10^7, 10^8.
Other Name: Immune cells
0.5 million units subcutaneously on Day -8 to Day -4.
Procedure: Stem Cell Infusion
Peripheral blood progenitor cells infused on Day 0 or on arrival of the unrelated donor cells.
5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 x 10/L for 3 consecutive days.
Starting dose of 0.015 mg/kg as a 24 hour continuous infusion daily adjusted with a goal to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after Day +90 if no GvHD is present.
Other Name: Prograf
5 mg/m2 administered intravenously on Days 1, 3, 6 and 11 post transplant.
- Maximum Tolerated Natural Killer (NK) Cell Dose [ Time Frame: 42 days ]Optimal NK cell dose determined in each of three distinct patient subgroups, A = KIR mismatched haplo donors, B = KIR mismatched cord blood donors, C = matched SIB donors. Same dose-finding design used within each subgroup. Four NK cell doses studied are: 106, 107, 3 x 107, and 108 NK cells. Cohorts of 2 patients used, starting at lowest NK cell dose level. Dose-limiting toxicity (DLT) defined as any of the events graft failure, severe (grade 3,4) infusional toxicity, severe grade 4 organ toxicity, or death by day 42.
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, MD, BS||713-792-8750|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Richard E. Champlin, MD, BS||M.D. Anderson Cancer Center|