Combination Chemotherapy, Monoclonal Antibody, and Natural Killer Cells in Treating Young Patients With Recurrent or Refractory Neuroblastoma
NCT ID: NCT01576692
Last Updated: 2018-11-15
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
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
34 participants
INTERVENTIONAL
2012-04-30
2018-10-17
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Clinical Trial on Autologous NK Cells Combined With GD2 Monoclonal Antibody in the Treatment of Children With Newly Diagnosed High-risk or Relapsed/Refractory Neuroblastoma
NCT06948994
Therapy for Children With Advanced Stage Neuroblastoma
NCT01857934
Phase I Study of 131-I mIBG Followed by Nivolumab & Dinutuximab Beta Antibodies in Children With Relapsed/Refractory Neuroblastoma
NCT02914405
Monoclonal Antibody Therapy in Treating Children With Metastatic Neuroblastoma in Second Remission
NCT00002458
Gene Therapy in Treating Children With Refractory or Recurrent Neuroblastoma
NCT00002748
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Primary Objective:
* To observe and describe the toxicities associated with humanized anti-GD2 antibody (hu14.18K322A) with and without allogeneic NK cells when given with repeated cycles of chemotherapy to children with refractory/relapsed neuroblastoma.
Secondary Objective:
* To describe response, time to progression, event-free and overall survival.
* To evaluate the feasibility of administering NK cells from a suitable donor after completion of the last dose of hu14.18K322A in three repeated cycles of chemotherapy
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Treatment
Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells.
Cells for infusion are prepared using the CliniMACS System.
Humanized anti-GD2 antibody
A maximum of 6 courses of therapy may be given on the following schedule:
* Courses 1, 3, and 5: Humanized anti-GD2 antibody + chemotherapy
* Courses 2, 4, and 6: Humanized anti-GD2 antibody + chemotherapy, with or without natural killer (NK) cells (depending on availability of appropriate NK donor)
* Humanized anti-GD2 antibody (hu14.18 K322A) dosage: 40 mg/m\^2)/dose, over 4 hours daily
* NK Cell dosage: minimum of 0.1 \* 10\^6 cells/kg; maximum of 400 \* 10\^6 CD45+ cells/kg, given once
Chemotherapy
Chemotherapy may include the following at the dosages shown below:
* cyclophosphamide: 400 mg/m\^2 IV days 1-5
* topotecan: 1.2 mg/m\^2 IV days 1-5
* temozolomide: 150 mg/m\^2 PO at least 1 hour before irinotecan
* irinotecan: 50 mg/m\^2 IV over 1 hour daily for 5 days
* carboplatin (AUC 8-dosing based on GFR), IV day 1 only
* ifosfamide: 2 g/m2 IV days 1-3
* etoposide: 100 mg/m2 days 1-3
Cytokines
Cytokines may be given at the following dosages:
* interleukin-2: 1 million units/m\^2 SQ beginning day 6 of each chemotherapy course and continued every other day for 6 doses
* GM-CSF: 250 mcg/m\^2/day beginning on day 7 or day 8 of chemotherapy course and continued daily through the nadir until ANC \>2,000/mm\^3
Natural killer cells
NK cells from haploidentical family donor will be infused on day 7 or 8, depending on course. NK cells may be infused in either the inpatient or outpatient setting by a physician, Physician Assistant, Nurse Practitioner, or qualified RN. Careful monitoring and supportive care during NK cell infusion will be guided in part by the Standard Operating Procedures for Lymphocytes Infusions in the St. Jude Nursing Policy \& Procedure Manual.
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
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Humanized anti-GD2 antibody
A maximum of 6 courses of therapy may be given on the following schedule:
* Courses 1, 3, and 5: Humanized anti-GD2 antibody + chemotherapy
* Courses 2, 4, and 6: Humanized anti-GD2 antibody + chemotherapy, with or without natural killer (NK) cells (depending on availability of appropriate NK donor)
* Humanized anti-GD2 antibody (hu14.18 K322A) dosage: 40 mg/m\^2)/dose, over 4 hours daily
* NK Cell dosage: minimum of 0.1 \* 10\^6 cells/kg; maximum of 400 \* 10\^6 CD45+ cells/kg, given once
Chemotherapy
Chemotherapy may include the following at the dosages shown below:
* cyclophosphamide: 400 mg/m\^2 IV days 1-5
* topotecan: 1.2 mg/m\^2 IV days 1-5
* temozolomide: 150 mg/m\^2 PO at least 1 hour before irinotecan
* irinotecan: 50 mg/m\^2 IV over 1 hour daily for 5 days
* carboplatin (AUC 8-dosing based on GFR), IV day 1 only
* ifosfamide: 2 g/m2 IV days 1-3
* etoposide: 100 mg/m2 days 1-3
Cytokines
Cytokines may be given at the following dosages:
* interleukin-2: 1 million units/m\^2 SQ beginning day 6 of each chemotherapy course and continued every other day for 6 doses
* GM-CSF: 250 mcg/m\^2/day beginning on day 7 or day 8 of chemotherapy course and continued daily through the nadir until ANC \>2,000/mm\^3
Natural killer cells
NK cells from haploidentical family donor will be infused on day 7 or 8, depending on course. NK cells may be infused in either the inpatient or outpatient setting by a physician, Physician Assistant, Nurse Practitioner, or qualified RN. Careful monitoring and supportive care during NK cell infusion will be guided in part by the Standard Operating Procedures for Lymphocytes Infusions in the St. Jude Nursing Policy \& Procedure Manual.
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
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Age \< 22 years at the time of enrollment.
* Measurable or evaluable (detectable by bone scan or MIBG, but not measurable) disease.
* Organ function: Must have adequate organ and marrow function as defined by the following parameters:
* Bone marrow: Absolute neutrophil count (ANC) \> 750/mm3; Platelets \> 75,000/mm3 (no platelet transfusions for at least 1 week)
* Hepatic: Total bilirubin ≤ 2 x upper limit of normal (ULN) for age; SGPT (ALT) ≤ 2.5 x ULN for age.
* Renal: Creatinine clearance or radioisotope GFR equal to or \>70 ml/min/1.73m2 OR serum creatinine based on age as follows:
* Age 5 years of age and under, then maximum serum creatinine 0.8 mg/dL
* Age \>5 and equal to or \<10 years, then maximum serum creatinine 1.0 mg/dL
* Age \>10 and equal to or \<15 years, then maximum serum creatinine 1.2 mg/dL
* Age \>15 years, then maximum serum creatinine 1.5 mg/dL
* Cardiovascular: Shortening fraction \> or equal to 27% by echocardiogram; Corrected QT interval \< or equal to 450 milliseconds
* Performance status: Karnofsky \> or equal to 50 for \> 10 years of age; Lansky \> or equal to 50 for children equal to or \< 10 years of age.
* Prior therapy: Participant must have fully recovered from the acute toxic effects of all prior therapy prior to enrolling on study.
* Myelosuppressive chemotherapy: Must not have received myelosuppressive therapy within 2 weeks prior to study entry (4 weeks if nitrosurea).
* Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with biologic agent, including retinoic acid. At least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody. Participants receiving IVIG are eligible; however, participant must not receive IVIG during the 4 days of antibody infusion.
* Radiation therapy: At least 2 weeks since prior local radiation therapy at the time of study entry.
* Growth factors: Must not have received hematopoietic growth factors (G-CSF, GM-CSF) for at least 1 week prior to study entry.
* Investigational agent: Must not have received investigational agent within 7 days of study entry.
* Immune therapy: Must not have received immunosuppressive (including glucocorticoids), immunostimulatory or any immunomodulatory treatment within 2 weeks of study entry. Steroid containing inhalers, steroid replacement for adrenal insufficiency and steroid premedication for prevention of transfusion or imaging contrast-agent related allergic reaction will be permitted.
* Participants may have had prior CNS metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by CT or MRI).
* Written informed consent following institutional and federal guidelines.
* Donor is a partially matched family member.
* Donor is HIV negative.
* Donor is at least 18 years of age.
* Donor is not pregnant.
* Donor does not have any other medical condition that, in the opinion of an independent physician, precludes performance of an apheresis procedure.
Exclusion Criteria
* Pregnancy or breast feeding: Study participants who are pregnant are not eligible for this study. Pregnancy tests must be obtained in girls who are \> 10 years of age or post-menarchal within 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during participation in the trial. Breast feeding should be discontinued if a mother wishes to participate in this study.
* Allergy: Known hypersensitivity to other recombinant human antibodies.
* An uncontrolled infection.
* Participants who have not started protocol therapy within 7 days of study enrollment.
21 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
CURE Childhood Cancer, Inc.
OTHER
St. Jude Children's Research Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Wayne L. Furman, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Countries
Review the countries where the study has at least one active or historical site.
Related Links
Access external resources that provide additional context or updates about the study.
St. Jude Children's Research Hospital
Clinical Trials Open at St. Jude
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2012-00495
Identifier Type: REGISTRY
Identifier Source: secondary_id
GD2NK
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.