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

April 23, 2014 updated by: St. Jude Children's Research Hospital

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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).
Procedure: Haploidentical donor derived natural killer cell infusion
Therapeutic cell infusion
Drug: Chemotherapy
Cyclophosphamide, Fludarabine, Interleukin-2, Mesna
Other Names:
  • cyclophosphamide: cytoxan
  • fludarabine: Fludara(R)
  • interleukin-2: IL-2, aldesleukin, Proleukin(R)
  • mesna: Mesnex(R)
Device: CliniMACS
Cell selection system based on magnetic-activated cell sorting

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
4 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Collaborators

National Cancer Institute (NCI)
Assisi Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

March 14, 2008

First Submitted That Met QC Criteria

March 20, 2008

First Posted (Estimate)

March 21, 2008

Study Record Updates

Last Update Posted (Estimate)

April 24, 2014

Last Update Submitted That Met QC Criteria

April 23, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NKEXP
  • R01CA113482 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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