- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00697671
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Strata A
Patients with ALL, CML, JMML, MDS, or NHL with bone marrow relapse after stem cell transplant.
|
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
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.
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.
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.
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.
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.
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.
|
Other: 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
|
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
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.
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.
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.
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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4 months post infusion
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
4 months infusion
|
To explore the efficacy of NK cell infusion in research participants with chemotherapy refractory hematologic malignancies
Time Frame: 4 months infusion
|
4 months infusion
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Wing Leung, MD, PhD, St. Jude Children's Research Hospital
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Lymphoid
- Neoplasms
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelomonocytic, Juvenile
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Cyclophosphamide
- Etoposide
- Clofarabine
- Interleukin-2
Other Study ID Numbers
- NKHEM
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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