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
NCT ID: NCT02130869
Last Updated: 2017-12-22
Study Results
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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COMPLETED
PHASE1
8 participants
INTERVENTIONAL
2014-10-10
2017-12-20
Brief Summary
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The investigators expect to enroll 36 participants. Haploidentical family members (donors) will also be recruited to provide natural killer cells.
Detailed Description
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* 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
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group A: Neuroblastoma
All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group A participants receive busulfan, melphalan, CD133+ selected autologous stem cell infusion, hu14.18K322A, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF.
Cells for infusion are prepared using the CliniMACS System.
CD133+ 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.
IL-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.
hu14.18K322A
Participants with neuroblastoma (Group A) will receive hu14.18K322A intravenously (IV).
Busulfan
Given IV - Group A only.
Melphalan
Given IV - All groups.
GM-CSF
Given SQ - All groups.
Haploidentical 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.
G-CSF
Given SQ - All Groups.
CliniMACS
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.
Group B: Lymphoma
All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group B participants receive bendamustine, etoposide (or etoposide phosphate), cytarabine, melphalan, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF.
Cells for infusion are prepared using the CliniMACS System.
CD133+ 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.
IL-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.
Melphalan
Given IV - All groups.
GM-CSF
Given SQ - All groups.
Bendamustine
Given IV - Group B only.
Etoposide
Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.
Cytarabine
Given IV - Group B only.
Haploidentical 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.
G-CSF
Given SQ - All Groups.
Etoposide phosphate
In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.
CliniMACS
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.
Group C: High-Risk Tumors
All participants first receive standard of care high-dose chemotherapy specific to their tumor type. Group C participants receive melphalan, etoposide (or etoposide phosphate), carboplatin, CD133+ selected autologous stem cell infusion, IL-2, haploidentical natural killer cell infusion, G-CSF, and GM-CSF.
Cells for infusion are prepared using the CliniMACS System.
CD133+ 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.
IL-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.
Melphalan
Given IV - All groups.
GM-CSF
Given SQ - All groups.
Etoposide
Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.
Carboplatin
Given IV - Group C only.
Haploidentical 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.
G-CSF
Given SQ - All Groups.
Etoposide phosphate
In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.
CliniMACS
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.
Interventions
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CD133+ 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.
IL-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.
hu14.18K322A
Participants with neuroblastoma (Group A) will receive hu14.18K322A intravenously (IV).
Busulfan
Given IV - Group A only.
Melphalan
Given IV - All groups.
GM-CSF
Given SQ - All groups.
Bendamustine
Given IV - Group B only.
Etoposide
Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.
Cytarabine
Given IV - Group B only.
Carboplatin
Given IV - Group C only.
Haploidentical 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.
G-CSF
Given SQ - All Groups.
Etoposide phosphate
In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.
CliniMACS
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
* 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.
21 Years
ALL
No
Sponsors
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St. Jude Children's Research Hospital
OTHER
Responsible Party
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Principal Investigators
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Brandon M. Triplett, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
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St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Countries
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Related Links
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St. Jude Children's Research Hospital
Clinical Trials Open at St. Jude
Other Identifiers
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NCI-2014-00275
Identifier Type: REGISTRY
Identifier Source: secondary_id
ASCIST
Identifier Type: -
Identifier Source: org_study_id