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

Primary Purpose

Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute, T-Cell, Juvenile Myelomonocytic Leukemia Lymphoblastic

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Haploidentical donor derived natural killer cell infusion
Chemotherapy
CliniMACS
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute focused on measuring Hematologic malignancies, non-B lineage, NK cell expansion, CliniMACS device, Immunotherapy

Eligibility Criteria

undefined - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
March 14, 2008
Last Updated
April 23, 2014
Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI), Assisi Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00640796
Brief Title
Pilot Study of Expanded, Donor Natural Killer Cell Infusions for Refractory Non-B Lineage Hematologic Malignancies and Solid Tumors
Official Title
Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Hematologic Malignancies and Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
National Cancer Institute (NCI), Assisi Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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).
Intervention Type
Procedure
Intervention Name(s)
Haploidentical donor derived natural killer cell infusion
Intervention Description
Therapeutic cell infusion
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Other Intervention Name(s)
cyclophosphamide: cytoxan, fludarabine: Fludara(R), interleukin-2: IL-2, aldesleukin, Proleukin(R), mesna: Mesnex(R)
Intervention Description
Cyclophosphamide, Fludarabine, Interleukin-2, Mesna
Intervention Type
Device
Intervention Name(s)
CliniMACS
Intervention Description
Cell selection system based on magnetic-activated cell sorting
Primary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Shook, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital

Learn more about this trial

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

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