Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies

This study has been completed.
Sponsor:
Collaborator:
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00697671
First received: April 14, 2008
Last updated: July 15, 2013
Last verified: July 2013

April 14, 2008
July 15, 2013
March 2007
February 2013   (final data collection date for primary outcome measure)
To assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants with chemotherapy refractory non-acute myelogenous leukemia (non-AML) hematologic malignancies [ Time Frame: 4 months post infusion ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00697671 on ClinicalTrials.gov Archive Site
  • To study the persistence, phenotype and function of donor natural killer (NK) cells after infusion in research participants with chemotherapy refractory hematologic malignancies. [ Time Frame: 4 months infusion ] [ Designated as safety issue: Yes ]
  • To explore the efficacy of NK cell infusion in research participants with chemotherapy refractory hematologic malignancies [ Time Frame: 4 months infusion ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies
Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies

The prognosis of pediatric patients with hematologic malignancies whose disease is primarily refractory or those who experience a chemotherapy resistant bone marrow relapse is extremely poor. When new agents or chemotherapeutic regimens are unable to induce remission in this patient population, hematopoietic stem cell transplant (HSCT) is also a poor alternative. Thus, in this very high risk group, additional attempts at remission induction with various combinations of chemotherapy alone will unlikely improve outcome and will contribute to overall toxicity. Alternative therapies are needed in these patients with chemotherapy resistant disease.

Immunotherapy with natural killer (NK) cell infusion has the potential to decrease toxicity and induce hematologic remission. NK cells can kill target cells, including leukemia cells, without prior exposure to those cells. In patients undergoing allogeneic HSCT, several studies have demonstrated the powerful effect of NK cells against leukemia. Furthermore, 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 effects. In this high risk group, complete leukemic remission has been observed in several of these patients after NK cell infusion.

With the current technology available at St. Jude, we have developed a procedure to purify NK cells from adult donors. This protocol will assess the safety of chemotherapy and IL-2 administration to facilitate transient NK-cell engraftment in research participants who have chemotherapy refractory hematologic malignancies including acute lymphoblastic leukemia, chronic myelogenous leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, or non-Hodgkin's lymphoma. In this same cohort, we will also intend to explore the efficacy of NK cells infused in those participants who have chemotherapy refractory disease.

This study will evaluate the persistence, phenotype and function of donor NK cells as well as exploring the efficacy of the infusion in research participants with chemotherapy refractory hematologic malignancies.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Lymphoblastic Leukemia
  • Chronic Myelogenous Leukemia
  • Juvenile Myelomonocytic Leukemia
  • Myelodysplastic Syndrome
  • Non-Hodgkin's Lymphoma
  • Other: NK Cell Infusion
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued
  • Biological: Immunotherapy
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
  • Device: Miltenyi Biotec CliniMACS device
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
  • Drug: Interleukin-2 (IL-2)
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
  • Drug: Clofarabine
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
  • Drug: Cyclophosphamide
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
  • Drug: Etoposide
    All participants will receive a 4 day regimen of chemotherapy (clofarabine, cyclophosphamide, and etoposide) followed by an infusion of HLA partially matched family member donor NK cells processed through the use of the investigational CliniMACS device. Interleukin-2 (IL-2) will be given three times per week post-infusion for a minimum of 2 weeks. IL-2 administration will continue until donor NK cells are no longer detectable in the recipient, and, at that time, will be discontinued.
  • Strata A
    Patients with ALL, CML, JMML, MDS, or NHL with bone marrow relapse after stem cell transplant.
    Interventions:
    • Other: NK Cell Infusion
    • Biological: Immunotherapy
    • Device: Miltenyi Biotec CliniMACS device
    • Drug: Interleukin-2 (IL-2)
    • Drug: Clofarabine
    • Drug: Cyclophosphamide
    • Drug: Etoposide
  • Strata B
    Patients with ALL, CML, JMML , MDS, or NHL with primary induction failure and persistent disease; or participants with relapsed ALL, CML, JMML, MDS, or NHL with persistent disease after re-induction
    Interventions:
    • Other: NK Cell Infusion
    • Biological: Immunotherapy
    • Device: Miltenyi Biotec CliniMACS device
    • Drug: Interleukin-2 (IL-2)
    • Drug: Clofarabine
    • Drug: Cyclophosphamide
    • Drug: Etoposide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
May 2013
February 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • At least two weeks since receipt of last biological therapy, chemotherapy, or radiation therapy.
  • Has a suitable adult family member donor available for NK cell donation.
  • No current pleural or pericardial effusion.
  • HIV negative
  • Adequate clinical standing as evidenced by being within multiple renal, hepatic, pulmonary, and neurological required testing parameters.

Exclusion Criteria:

  • Pregnant or lactating
Both
up to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00697671
NKHEM
No
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Assisi Foundation
Principal Investigator: Wing Leung, MD, PhD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP