Trial record 3 of 44 for:    IL-2 SELECT

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by St. Jude Children's Research Hospital
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT02130869
First received: May 1, 2014
Last updated: June 11, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Neuroblastoma
Lymphoma
High-risk Tumor
Device: CD133+ selected autologous stem cell infusion
Biological: IL-2
Biological: hu14.18K322A
Drug: Busulfan
Drug: Melphalan
Biological: GM-CSF
Drug: Bendamustine
Drug: Etoposide
Drug: Cytarabine
Drug: Carboplatin
Device: Haploidentical natural killer cell infusion
Biological: G-CSF
Drug: Etoposide phosphate
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Percent of participants with positive ANC engraftment [ Time Frame: Day 35 post transplant ] [ Designated as safety issue: Yes ]
    Feasibility 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 Outcome Measures:
  • Overall survival [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    Overall survival is defined based on any death. The Kaplan-Meier Estimate will be provided.

  • Disease-free survival [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    Disease-free survival is defined based on any death, graft failure, or relapsed/resistant disease. The Kaplan-Meier Estimate will be provided.

  • Incidence of relapse [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    Cumulative incidence of relapse will be estimated using Kalbfleisch-Prentice method. Death is the competing risk event.

  • Lymphocyte and hematopoietic reconstitution [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    The hematopoietic cell recovery and engraftment rates will be reported with a Blyth-Still-Casella 95% confidence interval.

  • Characteristics of the stem cell grafts [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    Results will be reported and presented descriptively.

  • Characteristics of the natural killer cell grafts. [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    Results will be reported and presented descriptively.

  • Overall survival of patients treated without stem cell manipulation or NK cell infusion due to off therapy criteria [ Time Frame: Up to one year after transplantation ] [ Designated as safety issue: No ]
    The Kaplan-Meier estimate will be provided for overall survival analysis.


Estimated Enrollment: 36
Study Start Date: September 2014
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Device: 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.
Other Name: Natural killer (NK) cell infusion
Biological: 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.
Other Names:
  • Interleukin-2
  • Aldesleukin
  • Proleukin(R)
Biological: hu14.18K322A
Participants with neuroblastoma (Group A) will receive hu14.18K322A intravenously (IV).
Other Names:
  • anti-GD2 antibody
  • Hu14.18K322MAB
Drug: Busulfan
Given IV - Group A only.
Other Names:
  • Busulfex(R)
  • Myleran(R)
Drug: Melphalan
Given IV - All groups.
Other Names:
  • L-phenylalanine mustard
  • Phenylalanine mustard
  • L-PAM
  • L-sarcolysin
Biological: GM-CSF
Given SQ - All groups.
Other Names:
  • Sargramostim
  • Leukine(R)
Device: 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.
Other Name: NK cell infusion
Biological: G-CSF
Given SQ - All Groups.
Other Names:
  • Filgrastim
  • Neupogen(R)
Experimental: 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.
Device: 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.
Other Name: Natural killer (NK) cell infusion
Biological: 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.
Other Names:
  • Interleukin-2
  • Aldesleukin
  • Proleukin(R)
Drug: Melphalan
Given IV - All groups.
Other Names:
  • L-phenylalanine mustard
  • Phenylalanine mustard
  • L-PAM
  • L-sarcolysin
Biological: GM-CSF
Given SQ - All groups.
Other Names:
  • Sargramostim
  • Leukine(R)
Drug: Bendamustine
Given IV - Group B only.
Other Names:
  • Treanda®
  • Bendamustine hydrochloride
Drug: Etoposide
Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.
Other Names:
  • VP-16
  • Vepesid(R)
Drug: Cytarabine
Given IV - Group B only.
Other Name: ARA-C
Device: 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.
Other Name: NK cell infusion
Biological: G-CSF
Given SQ - All Groups.
Other Names:
  • Filgrastim
  • Neupogen(R)
Drug: Etoposide phosphate
In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.
Other Name: Etopophos(R)
Experimental: 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.
Device: 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.
Other Name: Natural killer (NK) cell infusion
Biological: 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.
Other Names:
  • Interleukin-2
  • Aldesleukin
  • Proleukin(R)
Drug: Melphalan
Given IV - All groups.
Other Names:
  • L-phenylalanine mustard
  • Phenylalanine mustard
  • L-PAM
  • L-sarcolysin
Biological: GM-CSF
Given SQ - All groups.
Other Names:
  • Sargramostim
  • Leukine(R)
Drug: Etoposide
Given IV - Group B and Group C. In case of etoposide reactions, etoposide phosphate will be given.
Other Names:
  • VP-16
  • Vepesid(R)
Drug: Carboplatin
Given IV - Group C only.
Device: 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.
Other Name: NK cell infusion
Biological: G-CSF
Given SQ - All Groups.
Other Names:
  • Filgrastim
  • Neupogen(R)
Drug: Etoposide phosphate
In case of etoposide reactions, etoposide phosphate will be given IV. - Group B and Group C only.
Other Name: Etopophos(R)

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
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02130869

Contacts
Contact: Christine Hartford, MD 866-278-5833 referralinfo@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Christine Hartford, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Christine Hartford, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Christine Hartford, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT02130869     History of Changes
Other Study ID Numbers: ASCIST, NCI-2014-00275
Study First Received: May 1, 2014
Last Updated: June 11, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Autologous stem cell transplantation
Natural killer cells

Additional relevant MeSH terms:
Interleukin-2
Lymphoma
Neuroblastoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Bendamustine
Etoposide
Etoposide phosphate
Melphalan
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on June 28, 2015