Symptoms and General Pathology

All Conditions

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Blood and Lymph Conditions

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Rare Diseases

Syndrome

Lymphoma

Leukemia

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Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

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Leukemia, Myelomonocytic, Juvenile

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

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Antineoplastic Agents

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All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

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Interleukin-2

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

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).

Haploidentical donor derived natural killer cell infusion

Cyclophosphamide, Fludarabine, Interleukin-2, Mesna

Chemotherapy

Cell selection system based on magnetic-activated cell sorting

CliniMACS

David Shook, MD

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).

Secondary objectives include the evaluation of the in vivo lifespan and phenotype of the expanded NK cells and explore the efficacy of these donor NK cells in study participants with relapsed or refractory hematologic malignancies or sarcomas.

Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors

Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Hematologic Malignancies and Solid Tumors

National Cancer Institute (NCI)

Assisi Foundation

St. Jude Children's Research Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors	NCT00640796	Leukemia, Myelo... Leukemia, Lymph... Juvenile Myelom... T-cell Lymphobl... Myelodysplastic...	Haploidentical ... Chemotherapy CliniMACS	- 18 Years	St. Jude Children's Research Hospital
Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors	NCT00640796	Leukemia, Myelo... Leukemia, Lymph... Juvenile Myelom... T-cell Lymphobl... Myelodysplastic...	Haploidentical ... Chemotherapy CliniMACS	- 18 Years	St. Jude Children's Research Hospital

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