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A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas

A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02130869
Enrollment
8
Registered
2014-05-06
Start date
2014-10-10
Completion date
2017-12-20
Last updated
2017-12-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Neuroblastoma, Lymphoma, High-risk Tumor

Keywords

Autologous stem cell transplantation, Natural killer cells

Brief summary

This is a pilot clinical trial investigating the addition of haploidentical natural killer cell infusion to autologous stem cell transplantation. This intervention will be evaluated in children with high-risk solid tumors for whom autologous transplantation is indicated. Natural killer cells from a haploidentical family member will be given after high dose chemotherapy and positively selected autologous stem cells. In patients with neuroblastoma, the anti-GD2 antibody hu14.18K322A will also be given. The effect on normal hematopoietic cell recovery will be evaluated and survival of children treated with this approach will be determined. The investigators expect to enroll 36 participants. Haploidentical family members (donors) will also be recruited to provide natural killer cells.

Detailed description

Primary Objective: * To evaluate day +35 ANC engraftment in autologous stem cell transplantation for high risk pediatric malignancies after stem cell selection and immunotherapy. Secondary Objectives * To estimate incidence of relapse, disease-free survival and overall survival. * To characterize lymphocyte and hematopoietic reconstitution in these patients. * To describe the characteristics of the stem cell and natural killer cell grafts. * To estimate the overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteria

Interventions

BIOLOGICALCD133+ selected autologous stem cell infusion

Hematopoietic stem cells will be collected from children with high-risk solid tumors. After collection, they will be immuno-magnetically selected using CD133 as a marker in efforts to reduce tumor cell contamination in the stem cell graft. After high dose chemotherapy, those selected stem cells will be infused, followed shortly thereafter by an infusion of haploidentical natural killer cells.

BIOLOGICALIL-2

Following infusion of haploidentical natural killer cells, interleukin-2 (IL-2) subcutaneously (SQ) will be given to support the in vivo survival of donor NK cells.

BIOLOGICALhu14.18K322A

Participants with neuroblastoma (Group A) will receive hu14.18K322A intravenously (IV).

DRUGBusulfan

Given IV - Group A only.

DRUGMelphalan

Given IV - All groups.

BIOLOGICALGM-CSF

Given SQ - All groups.

DRUGBendamustine

Given IV - Group B only.

DRUGEtoposide

Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.

DRUGCytarabine

Given IV - Group B only.

DRUGCarboplatin

Given IV - Group C only.

DEVICEHaploidentical natural killer cell infusion

NK cell product will be collected from donors using leukapheresis procedures. The autologous hematopoietic stem cell graft product will be positively selected using the investigational CliniMACS device and CD133 Microbead reagent. Following standard laboratory procedures, the NK cell product will be enumerated and assessed for viable cell content. NK cells will be infused by slow IV push over 3 to 15 minutes immediately after processing, evaluation and release testing.

BIOLOGICALG-CSF

Given SQ - All Groups.

DRUGEtoposide phosphate

In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.

DEVICECliniMACS

The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

Sponsors

St. Jude Children's Research Hospital
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No

Inclusion criteria

The transplant recipient will be evaluated for eligibility at two time points during study participation. The first phase will be when the autologous stem cell product is collected. The recipient will later need to meet specific eligibility criterion at the time of the autologous stem cell infusion. The two phases and the respective criteria are described below. Inclusion criteria for autologous stem cell collection (Phase 1 - transplant recipient): * Less than or equal to 21 years of age. * Malignancy at high risk of treatment failure for which autologous hematopoietic stem cell transplantation is considered within standard practice. * Group A: High-risk neuroblastoma * Group B: Recurrent or refractory Hodgkin lymphoma; recurrent or refractory non-Hodgkin lymphoma * Group C: High-risk, recurrent or metastatic sarcoma; recurrent or advanced stage Wilms tumor; desmoplastic small round cell tumor; metastatic or recurrent retinoblastoma, high-risk germ cell tumors, and high-risk brain tumors * Sarcoma or Wilms tumor diagnosis (Group C) will require evaluation by physician in the St. Jude Solid Tumor Division, other than the referring physician, attesting that autologous SCT provides the prospect of direct benefit for the participant. * Has a potentially suitable human leukocyte antigen (HLA) haploidentical donor available. * Research participant or legal guardian/representative must be willing to give written informed consent * Does not have any active or prior malignant or pre-malignant condition of the bone marrow, excluding metastasis of the primary malignancy. * Has no known allergy to murine products or positive human anti-mouse antibody (HAMA). * (Female only) Negative serum or urine pregnancy test (to be conducted within 7 days prior to enrollment). * (Female only) Not breastfeeding. Inclusion criteria to proceed with autologous stem cell transplantation (Phase 2 - transplant recipient): * Has a confirmed suitable HLA haploidentical donor available. * Previously collected autologous stem cell product met the minimum collection target and minimum infusion target as described in the protocol. * At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy. * Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic toxicities from prior therapy per the judgment of the PI. * Shortening fraction greater than or equal to 25%. * Creatinine clearance or glomerular filtration rate greater than or equal to 50 mL/min/1.73 m\^2. * Pulse oximetry greater than or equal to 92% on room air. * Alanine aminotransferase (ALT) and aspartate transaminase (AST) less than or equal to 3 times the upper limit of the institution-established normal range. * Direct bilirubin less than or equal to 3.0 mg/dL. * Karnofsky or Lansky performance score of greater than or equal to 50. * Has not received a prior hematopoietic stem cell transplant within 3 months. * Has no known allergy to murine products or positive human anti-mouse antibody (HAMA) * (Female only) Is not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to admission for transplant). * (Female only) Is not breastfeeding. * Does not meet donation eligibility requirements as outlined by 21 CFR 1271 and agency guidance. Inclusion criteria for haploidentical NK cell donor: * At least 18 years of age. * Partially HLA matched family member. * Human immunodeficiency virus (HIV) negative. * (Female only) Is not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment). * (Female only) Is not breastfeeding.

Design outcomes

Primary

MeasureTime frameDescription
Percent of participants with positive ANC engraftmentDay 35 post transplantFeasibility will be determined based on ANC engraftment defined as ANC ≥500/mm\^3 for 3 consecutive tests performed on different days evaluated before day 35 post-transplant. If the study is considered feasible, the ANC engraftment rate will be 100% (95% Blyth-Still-Casella (BSC) CI: 76.45%-100%) without any failure, 92% (BSC 95% CI: 65.11%-99.57%) with 1 failure, and 83% (BSC 95% CI: 55%-96.95%) with 2 failures. In addition, if more than 2 (≥ 3) on-therapy patients die due to any protocol treatment-related causes during the first 12 months post-transplant across all groups (3 deaths among 36 participants), the study will be stopped. Deaths due to treatment not specified in this protocol will not be included in evaluation of this stopping rule.

Secondary

MeasureTime frameDescription
Disease-free survivalUp to one year after transplantationDisease-free survival is defined based on any death, graft failure, or relapsed/resistant disease. The Kaplan-Meier Estimate will be provided.
Incidence of relapseUp to one year after transplantationCumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event.
Lymphocyte and hematopoietic reconstitutionUp to one year after transplantationThe hematopoietic cell recovery and engraftment rates will be reported with a Blyth-Still-Casella 95% confidence interval.
Overall survivalUp to one year after transplantationOverall survival is defined based on any death. The Kaplan-Meier Estimate will be provided.
Characteristics of the natural killer cell grafts.Up to one year after transplantationResults will be reported and presented descriptively.
Overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteriaUp to one year after transplantationThe Kaplan-Meier estimate will be provided for overall survival analysis.
Characteristics of the stem cell graftsUp to one year after transplantationResults will be reported and presented descriptively.

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026