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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2013-05-31

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Acute Lymphoblastic Leukemia Chronic Myelogenous Leukemia Juvenile Myelomonocytic Leukemia Myelodysplastic Syndrome Non-Hodgkin's Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Strata A

Patients with ALL, CML, JMML, MDS, or NHL with bone marrow relapse after stem cell transplant.

Group Type OTHER

NK Cell Infusion

Intervention Type OTHER

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

Immunotherapy

Intervention Type BIOLOGICAL

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.

Miltenyi Biotec CliniMACS device

Intervention Type 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.

Interleukin-2 (IL-2)

Intervention Type DRUG

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.

Clofarabine

Intervention Type DRUG

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.

Cyclophosphamide

Intervention Type DRUG

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.

Etoposide

Intervention Type DRUG

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 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

Group Type OTHER

NK Cell Infusion

Intervention Type OTHER

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

Immunotherapy

Intervention Type BIOLOGICAL

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.

Miltenyi Biotec CliniMACS device

Intervention Type 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.

Interleukin-2 (IL-2)

Intervention Type DRUG

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.

Clofarabine

Intervention Type DRUG

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.

Cyclophosphamide

Intervention Type DRUG

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.

Etoposide

Intervention Type DRUG

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.

Interventions

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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

Intervention Type OTHER

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.

Intervention Type BIOLOGICAL

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.

Intervention Type DEVICE

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.