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

NCT00640796 | Completed Phase 1

• 2 other identifiers: NKEXPR01CA113482
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Acute, T-Cell; Juvenile Myelomonocytic Leukemia Lymphoblastic; T-cell Lymphoblastic Lymphoma; Myelodysplastic Syndrome

Keywords

Hematologic malignancies, non-B lineage; NK cell expansion; CliniMACS device; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose of expanded NK cells in research participants with relapsed or refractory hematologic malignancies and sarcomas.

  4 Years

Study Arms (1)

Treatment

EXPERIMENTAL

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; Drug: Chemotherapy; Device: CliniMACS

Interventions

Haploidentical donor derived natural killer cell infusion PROCEDURE

Therapeutic cell infusion

Treatment

Chemotherapy DRUG

Cyclophosphamide, Fludarabine, Interleukin-2, Mesna

Also known as: cyclophosphamide: cytoxan, fludarabine: Fludara(R), interleukin-2: IL-2, aldesleukin, Proleukin(R), mesna: Mesnex(R)

Treatment

CliniMACS DEVICE

Cell selection system based on magnetic-activated cell sorting

Treatment

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Less than or equal to 18 years of age (may be greater than 18 years of age if currently a St. Jude patient).
• Patients with relapsed or refractory AML, T-ALL/T-LL, mixed lineage leukemia, CML, JMML, MDS, ESFT or RMS who are not eligible for SCT and have persistent disease after remission induction(s) therapy as evidenced by bone marrow morphology, cytogenetics, flow cytometry, molecular pathology, and/or restaging scans.
• At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.
• Shortening fraction greater than or equal to 25%.
• Creatinine clearance or glomerular filtration rate greater than or equal to 50 cc/min/1.73 m\^2.
• Pulse oximetry greater than or equal to 92% on room air.
• Direct bilirubin less than or equal to 3.0 mg/dL.
• Karnofsky or Lansky performance score of greater than or equal to 50.
• No known allergy to murine products or HAMA testing results within normal limits.
• Does not have a current pleural or pericardial effusion.
• Has a suitable adult family member donor available for NK cell donation.
• Is not receiving more than the equivalent of prednisone 10 mg daily.
• Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
• Not breast feeding.
• Eligibility criteria prior to initiation of protocol therapy (preparative regimen)

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• National Cancer Institute (NCI): collaborator
• Assisi Foundation: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Hematologic Neoplasms

Interventions

Drug Therapy; Cyclophosphamide; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• David Shook, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2008
• First Posted: March 21, 2008
• Study Start: September 1, 2008
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: April 24, 2014

Record last verified: 2014-04

Locations

US (1)