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

This study has been completed.
Sponsor:
Collaborators:
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00640796
First received: March 14, 2008
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Leukemia, Myeloid, Acute
Leukemia, Lymphocytic, Acute, T-Cell
Juvenile Myelomonocytic Leukemia Lymphoblastic
T-cell Lymphoblastic Lymphoma
Myelodysplastic Syndrome
Procedure: Haploidentical donor derived natural killer cell infusion
Drug: Chemotherapy
Device: CliniMACS
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Non-B Lineage Hematologic Malignancies and Solid Tumors

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: September 2008
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640796

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Assisi Foundation
Investigators
Principal Investigator: David Shook, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00640796     History of Changes
Other Study ID Numbers: NKEXP, R01CA113482
Study First Received: March 14, 2008
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Hematologic malignancies, non-B lineage
NK cell expansion
CliniMACS device
Immunotherapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Precancerous Conditions
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Interleukin-2
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on October 30, 2014