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

NCT ID: NCT00640796

Last Updated: 2014-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2014-04-30

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).

Detailed Description

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

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).

Group Type: EXPERIMENTAL

Haploidentical donor derived natural killer cell infusion

Intervention Type: PROCEDURE

Therapeutic cell infusion

Chemotherapy

Intervention Type: DRUG

Cyclophosphamide, Fludarabine, Interleukin-2, Mesna

CliniMACS

Intervention Type: DEVICE

Cell selection system based on magnetic-activated cell sorting

Interventions

Haploidentical donor derived natural killer cell infusion

Therapeutic cell infusion

Intervention Type: PROCEDURE

Chemotherapy

Cyclophosphamide, Fludarabine, Interleukin-2, Mesna

Intervention Type: DRUG

CliniMACS

Cell selection system based on magnetic-activated cell sorting

Intervention Type: DEVICE

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

• 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)

• Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal.
• Aspartate transaminase (AST) is no more than 2 times the upper limit of normal.
• Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the principal investigator

Eligibility criteria (NK cell DONOR):

• Family member with a greater than or equal to 3 of 6 HLA match to recipient.
• At least 18 years of age.
• HIV negative.
• Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
• Not breast feeding.

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Assisi Foundation

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Shook, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

Other Identifiers

R01CA113482

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NKEXP

Identifier Type: -

Identifier Source: org_study_id