Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00640796|
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : April 24, 2014
Modern frontline therapy for patients with hematologic malignancies is based on intensive administration of multiple drugs. In patients with relapsed disease, response to the same drugs is generally poor, and dosages cannot be further increased without unacceptable toxicities. For most patients, particularly those who relapse while still receiving frontline therapy, the only therapeutic option is hematopoietic stem cell transplantation (SCT). For those who relapse after transplant, or who are not eligible for transplant because of persistent disease, there is no proven curative therapy.
There is mounting evidence that NK cells have powerful anti-leukemia activity. In patients undergoing allogeneic SCT, several studies have demonstrated NK-mediated anti-leukemic activity. NK cell infusions in patients with primary refractory or multiple-relapsed leukemia have been shown to be well tolerated and void of graft-versus-host disease (GVHD) effects. Myeloid leukemias are particularly sensitive to NK cells cytotoxicity, while B-lineage acute lymphoblastic leukemia (ALL) cells are often NK-resistant. We have developed a novel method to expand NK cells and enhance their cytotoxicity. Expanded and activated donor NK cells have shown powerful anti-leukemic activity against acute myeloid leukemia (AML) cells and T-lineage ALL cells in vitro and in animal models of leukemia.
The present study represents the translation of these laboratory findings into clinical application.We propose to determine the safety of infusing expanded NK cells in pediatric patients who have chemotherapy refractory or relapse hematologic malignancies including AML, T-lineage ALL, T-cell lymphoblastic lymphoma (T-LL), chronic myelogenous leukemia (CML), juvenile myelomonocytic leukemia (JMML),myelodysplastic syndrome (MDS), Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS). The NK cells used for this study will be obtained from the patient's family member who will be a partial match to the patient's immune type (HLA type).
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myeloid, Acute Leukemia, Lymphocytic, Acute, T-Cell Juvenile Myelomonocytic Leukemia Lymphoblastic T-cell Lymphoblastic Lymphoma Myelodysplastic Syndrome||Procedure: Haploidentical donor derived natural killer cell infusion Drug: Chemotherapy Device: CliniMACS||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Hematologic Malignancies and Solid Tumors|
|Study Start Date :||September 2008|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||April 2014|
Participants undergo haploidentical donor derived natural killer cell infusion (cells obtained from donors and selected using CliniMACS cell selection system) and chemotherapy (cyclophosphamide, fludarabine, interleukin-2, mesna).
Procedure: Haploidentical donor derived natural killer cell infusion
Therapeutic cell infusion
Cyclophosphamide, Fludarabine, Interleukin-2, Mesna
Cell selection system based on magnetic-activated cell sorting
- To determine the maximum tolerated dose of expanded NK cells in research participants with relapsed or refractory hematologic malignancies and sarcomas. [ Time Frame: 4 Years ]
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): NCT00640796
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||David Shook, MD||St. Jude Children's Research Hospital|