Clinical trial NCT00697671: Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies
Official title: Pilot Study of Haploidentical Natural Killer Cell Infusions for Poor Prognosis Non-AML Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
Juvenile Myelomonocytic Leukemia
Myelodysplastic Syndrome
Non-Hodgkin's Lymphoma
Keywords: NK cell infusion
Immunotherapy
hematologic malignancy
Miltenyi Biotec device
haploidentical donor
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Assisi Foundation
First posted: 2008-06-16
Enrollment: 48
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
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
timeFrame: 4 months post infusion
Secondary outcomes:
measure: To study the persistence, phenotype and function of donor natural killer (NK) cells after infusion in research participants with chemotherapy refractory hematologic malignancies.
timeFrame: 4 months infusion
measure: To explore the efficacy of NK cell infusion in research participants with chemotherapy refractory hematologic malignancies
timeFrame: 4 months infusion
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Wing Leung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: