Phase 1 N=34 Treatment

A Phase I Study of NK Cell Infusion Following Allogeneic Peripheral Blood Stem Cell Transplantation From Related or Matched Unrelated Donors in Pediatric Patients With Solid Tumors and Leukemias

Leukemia · Lymphoma

Bottom Line

View on ClinicalTrials.gov: NCT01287104 ↗

Enrolled (actual)

Serious AEs

32.4%

Results posted

Aug 2019

Primary outcome: Primary: Number of Patients Who Received 2 Doses of Natural Killer (NK) Cell Infusions — 3; 2; 5 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Natural Killer (NK) Cell Infusion (Biological); Stem Cell Infusion (Biological)
Age: Pediatric, Adult · 4+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Jun 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Patients Who Received 2 Doses of Natural Killer (NK) Cell Infusions	3; 2; 5	—
PRIMARY Number of Patients Who Received the Highest Dose Level of NK Cells (1x10^6 NK Cells/kg for Patients With Related Donors and 1 x10^5 NK Cells/kg for Patients With Unrelated Donors) With Sustained Donor Lymphoid Engraftment	1; 5	—
SECONDARY Number of Participants With Mild, Moderate and/or Severe Chronic Graft Versus Host Disease (cGVHD)	0; 0; 2; 0; 0; 0	—
SECONDARY Disease-free Survival	2.8; 8.7; 10.35	—
SECONDARY Overall Survival Since Date of Transplant	15.5; 34; 10.5	—
SECONDARY Number of Occurrences of Viral Infection and/or Reactivation in Allogeneic Peripheral Blood Stem Cell Transplant (PBSCT) Followed by Natural Killer-donor Lymphocyte Infusion (NK-DLI)	6; 11; 14	—
SECONDARY Number of Participants With a Decline in Interleukin 7 (IL-7) and Interleukin 15 (IL-15) Cell Numbers Post-Transplant	—	—
SECONDARY Number of Participants With Presence of Killer-cell Immunoglobulin-like Receptors (KIR) Gene Mismatch	3; 2; 5	—
SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	4; 7; 12; 8	—

Summary

Background: * Bone marrow stem cells, which are found in the bone marrow and blood stream, can be collected and transplanted to treat a variety of types of cancer in a process known as hematopoietic stem cell transplantation (HSCT). When stem cells are taken from one person, most commonly a sibling or a family member, and then given to another person, this is referred to as allogeneic HSCT. Allogeneic HSCT has proven to be an especially effective treatment for patients with some types of cancers of the blood (leukemia) and certain solid tumors. The transplanted stem cells travel to the patient's bone marrow and begin producing normal blood cells, and also attack patients cancer cells. * Because allogenic HSCT does not always prevent the cancer from returning, researchers are interested in determining whether another type of immune cell taken from the stem cell donors white blood cells, called a "natural killer" (NK) cell, can be given in addition to the HSCT to help fight the tumor. In the laboratory, NK cells have been shown to kill tumor cells, but it is not yet know if this will occur when given to patients after HSCT. Objectives: * To determine the safety, effectiveness, and immune system response of giving NK white blood cells to individuals who have received allogeneic HSCT. * To identify possible side effects from the treatment. Eligibility: * Donors: Stem cell donors whose blood matches one of the recipients on six out of six human leukocyte antigen (HLA) (blood immune marker) types. The donor may not be the identical twin of a recipient. * Recipients: Individuals between 4 and 35 years of age who have been diagnosed with pediatric solid tumors that have not responded to standard treatment, or individuals between 4 and 18 years of age who have been diagnosed with leukemia that has not responded to standard treatment. * Other eligibility requirements which include a physical exam and blood laboratory evaluation are included to make sure it is safe for both the donor to donate and the recipient to undergo the transplant procedure. Design: * Donors and recipients will be screened with a full medical history and physical examination, and will provide blood and urine samples; recipients will have tumor imaging studies and other tests as required by the researchers. * Donors: * Participants will receive filgrastim injections (to stimulate the bone marrow) for 1 week to make stem cells travel from bone marrow to blood. * Participants will provide stem cells and NK cells through apheresis. * Recipients: * Participants will have three cycles of chemotherapy to treat the underlying cancer and weaken the immune system so that it will accept the donor cells. * Participants will then receive preparative chemotherapy for the transplant and two days after the last dose of chemotherapy, participants will have allogenic HSCT using the donated stem cells. * Participants will receive an infusion of NK cells on days 7 and 35 after the HSCT. - Participants will remain in the hospital for monitoring after the HSCT and NK cell treatments, and will be followed closely as outpatients for the first 6 months after the transplant and then less frequently for at least 5 years.

Eligibility Criteria

INCLUSION CRITERIA: PATIENTS (RECIPIENT)
Hematologic Malignancies Diagnoses:
Acute lymphoblastic leukemia (ALL) with a history of bone marrow relapse in clinical remission (CR) #2 or greater, or in CR#1 if prior induction failure; or with an M1 marrow if unable to achieve CR.
Philadelphia chromosome positive ALL patients who;
Have progressed through or relapsed following tyrosine kinase inhibitor (TKI) therapy or conventional myeloablative therapy

Are ineligible to receive tyrosine kinase inhibitor (TKI) therapy AND myeloablative hematopoietic stem cell transplant (HSCT)
Acute Myelogenous Leukemia (AML) with a history of bone marrow relapse in remission CR #2 or greater; or with an M1 marrow if unable to achieve CR; or in CR#1 if prior induction failure; or any of the following High-Risk categories:
Fms-related tyrosine kinase 3 (FLT3)/internal tandem duplication (ITD)+ with high allelic ratio > 0.4 (high allelic ration (HR) FLT3/ITD+) regardless of low risk features.
Presence of monosomy 7, monosomy 5, or del5q, without inv(16)/t(16;16) or t(8;21) cytogenetics or NPM or CEBP(alpha) mutations.
Acute myelogenous leukemia (AML) without inv(16)/t(16;16), t(8;21), nucleophosmin (NPM), CCAAT/enhancer binding protein (CEPB)(alpha) mutations, monosomy 7, monosomy 5, del5q, or HR FLT3/ITD+, but with evidence of residual AML (greater than or equal to 0.1%) at end of Induction I.
Hodgkin's and Non-Hodgkin's Lymphoma with refractory disease or relapse after at least one salvage regimen, or after autologous stem cell transplant
Juvenile Myelocytic Leukemia (JMML) with less than 10% blasts in marrow and blood, who are not eligible for effective standard therapies.
Age: 4 to less than or equal to 35 years old at the time of enrollment for solid tumor patients and 4 to less than or equal to 35 years old for hematologic malignancies.
All previous cytotoxic chemotherapy must be completed at least 3 weeks prior to study entry. Any prior non-hematologic vital organ toxicity (cardiac, pulmonary, hepatic, renal) of any previous therapy must have resolved to grade 1 or less, unless specified elsewhere in Inclusion Criteria for Patient (Recipient).

EXCEPTIONS:

There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects; or

Subjects receiving standard acute lymphoblastic leukemia (ALL) maintenance chemotherapy will not require washout.

All previous immunologic or molecularly targeted therapy must be completed at least 1 week prior to study entry. Any prior non-hematologic toxicity of any previous therapy must have resolved to grade 1 or less, unless specified elsewhere in Inclusion Criteria for Patient (Recipient).
Prior investigational therapy must be completed at least 30 days prior to study entry
Patients with prior autologous or allogeneic transplant are eligible. Patients must be greater than 100 days post transplant and have no evidence of active graft versus host disease (GVHD).
Performance status: Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2, or for children less than or equal to 10 years of age, Lansky greater than or equal to 60. Life expectancy greater than 3 months.
Availability of human leukocyte antigen (HLA)-matched (5-6/6 antigen or 8/8 allele) related or unrelated donor.
Cardiac function: Left ventricular ejection fraction greater than or equal to 45% by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO), fractional shortening greater than or equal to 28% by ECHO.
Pulmonary function: Diffusing capacity of the lungs for carbon monoxide (DLCO) >= 40% of the expected value corrected for alveolar volume and hgb for reduced intensity transplant and DLCO >=55% for myeloablative regimen. For children who are unable to cooperate for pulmonary function tests (PFTs), the criterion is: No evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen thera

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Data sourced from ClinicalTrials.gov (NCT01287104). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.