NeuroblastomaPhase 1NCT00877110
Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
A Phase 1 study testing cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8 in people with Neuroblastoma and Bone Marrow, Sympathetic Nervous System, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
Funding Source - FDA OOPD FDR004128 The goal of this study is to see if it is safe and feasible to give chemotherapy, natural killer (NK) cells, and an antibody called 3F8. The NK cells must come from a family member who shares half of the HLA proteins which are immune proteins important in transplant. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neuroblastoma, Bone Marrow, Sympathetic Nervous System
- What is being tested?
- cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Apr 2009to 7 Jan 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the MSKCC Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
- High-risk NB as defined by risk-related treatment guidelines and the International NB Staging System,57 i.e., stage 4 with (any age) or without (>365 days of age) MYCN amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified stage 4S.
- Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy.
- Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy.
- Disease staging approximately within one month of treatment.
- Human anti-mouse antibody (HAMA) titer <1000 Elisa units/ml if applicable
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- Available autologous stem cells: ≥2 x 106 CD34+ cells/kg
- Adequate cardiac function as measured by echocardiogram
- Eligible NK donor
- Signed informed consent indicating awareness of the investigational nature of this program.
- Donor Eligibility
- Donor is blood-related and HLA-haploidentical to the recipient.
- Donor has undergone serologic testing for transmissible diseases as per blood banking guidelines for organ and tissue donors. Tests include but are not limited to: HepBsAg, HepBsAb, HepBcAb, HepC antibody, HIV, HTLV I and II, VZV, CMV and VDRL, West Nile Virus and Chagas screen. Donor must have normal negative test results for HIV, HTLV I and II, and West Nile Virus. Donor exposure to other viral pathogens will be discussed on a case-by-case basis by the investigators.
- Donor must be able to undergo leukopheresis for total volume of 10-15 liters.
- There is no age restriction for the donor.
Who cannot join
- Patients with CR/VGPR disease
- Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity > or = to grade 3 except for hearing loss, alopecia, anorexia, nausea, hyperbilirubinemia and hypomagnesemia from TPN, which may be grade 3
- ANC should be >500/uL; platelet count >25K/uL.
- History of allergy to mouse proteins
- Active life-threatening infection
- HAMA titer >1000 Elisa units/ml
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- Inability to comply with protocol requirements
- Donor Exclusion Criteria
- Cardiac risk factors precluding ability to undergo leukopheresis
- Concurrent malignancy or autoimmune disease
- Donor is pregnant.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
Funding Source - FDA OOPD FDR004128
The goal of this study is to see if it is safe and feasible to give chemotherapy, natural killer (NK) cells, and an antibody called 3F8. The NK cells must come from a family member who shares half of the HLA proteins which are immune proteins important in transplant. NK cells are a type of white blood cell. They can recognize and kill abnormal cells in the body and can work together with antibodies to kill target cells. The antibody 3F8 specifically recognizes a protein present on the target cancer cell.
- Being tested
- cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8
- Keywords
- BETA-D-GLUCAN, CYCLOPHOSPHAMIDE (CYTOXAN), MAB 131 I - 3F8, TOPOTECAN, VINCRISTINE, Neuroblastoma, 09-011
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8Drug
Patients will receive combination chemotherapy with intravenous (IV) cyclophosphamide 70mg/kg/day (for patients with body weight<70kg) or 2100mg/m2/day (for patients with body weight ≥70kg) for two days, IV vincristine 0.067mg/kg or 2mg/m2/day (lower of the two doses to be chosen; maximum 2mg) for one day, and IV topotecan 2.4 mg/m2/day for 3 days during their first cycle. If receiving a second and/or third cycle, the only chemotherapy patients will receive is cyclophosphamide at 50 mg/kg/day for 2 days. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor. On day +3, the patient will start daily infusion of 3F8 for 5 days. The treatment schedule may require minor adjustment by ±1 day as clinically indicated (e.g. due to PDH closure for holidays or due to inclement weather).
| Study group | Role | What they receive |
|---|---|---|
| chemotherapy, allogeneic NK cells, 3F8 | Experimental | This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with 3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups of 3 patients/dose of NK cells. Four dose levels of NK cells, starting at dose level I, will be evaluated in this treatment protocol. In the unlikely case toxicity is encountered at dose level I, patients will then be treated at the lower dose level 0. Patients can receive up to 3 cycles of treatment on protocol. For subsequent cycles, patients will be treated at either less than or at the same dose level of NK cells as their first cycle. Receives: Drug: cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB
Measured: 3 years
Secondary outcomes (3)
Estimate the anti-NB effect of allogeneic NK infusions plus 3F8
Measured: 3 years
Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8
Measured: 3 years
Assess the relationship between CD16 polymorphism and ADCC in vitro
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2009 (estimated)
- Study start2 Apr 2009
- Primary completion7 Jan 2019
- Study completion7 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shakeel Modak, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00877110
- Sponsor's protocol ID
- 09-011
- Other IDs
- MSKCC09011 FDR004128
- Status last verified
- Jan 2019
- First submitted
- 6 Apr 2009
- Last updated
- 10 Jan 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma
- ClinicalTrials.gov ID
- NCT00877110
- Acronym / sponsor ID
- 09-011
- Keywords
- BETA-D-GLUCAN, CYCLOPHOSPHAMIDE (CYTOXAN), MAB 131 I - 3F8, TOPOTECAN, VINCRISTINE, Neuroblastoma, 09-011
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 2 Apr 2009 (actual)
- Primary completion
- 7 Jan 2019 (actual)
- Study completion
- 7 Jan 2019 (actual)
- First posted
- 7 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Funding Source - FDA OOPD FDR004128
The goal of this study is to see if it is safe and feasible to give chemotherapy, natural killer (NK) cells, and an antibody called 3F8. The NK cells must come from a family member who shares half of the HLA proteins which are immune proteins important in transplant. NK cells are a type of white blood cell. They can recognize and kill abnormal cells in the body and can work together with antibodies to kill target cells. The antibody 3F8 specifically recognizes a protein present on the target cancer cell.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| chemotherapy, allogeneic NK cells, 3F8 | Experimental | Drug: cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with 3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups of 3 patients/dose of NK cells. Four dose levels of NK cells, starting at dose level I, will be evaluated in this treatment protocol. In the unlikely case toxicity is encountered at dose level I, patients will then be treated at the lower dose level 0. Patients can receive up to 3 cycles of treatment on protocol. For subsequent cycles, patients will be treated at either less than or at the same dose level of NK cells as their first cycle. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the MSKCC Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
- High-risk NB as defined by risk-related treatment guidelines and the International NB Staging System,57 i.e., stage 4 with (any age) or without (>365 days of age) MYCN amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified stage 4S.
- Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy.
- Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy.
- Disease staging approximately within one month of treatment.
Key exclusion criteria (11 listed)
- Patients with CR/VGPR disease
- Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity > or = to grade 3 except for hearing loss, alopecia, anorexia, nausea, hyperbilirubinemia and hypomagnesemia from TPN, which may be grade 3
- ANC should be >500/uL; platelet count >25K/uL.
- History of allergy to mouse proteins
- Active life-threatening infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8Patients will receive combination chemotherapy with intravenous (IV) cyclophosphamide 70mg/kg/day (for patients with body weight<70kg) or 2100mg/m2/day (for patients with body weight ≥70kg) for two days, IV vincristine 0.067mg/kg or 2mg/m2/day (lower of the two doses to be chosen; maximum 2mg) for one day, and IV topotecan 2.4 mg/m2/day for 3 days during their first cycle. If receiving a second and/or third cycle, the only chemotherapy patients will receive is cyclophosphamide at 50 mg/kg/day for 2 days. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor. On day +3, the patient will start daily infusion of 3F8 for 5 days. The treatment schedule may require minor adjustment by ±1 day as clinically indicated (e.g. due to PDH closure for holidays or due to inclement weather). | Drug | chemotherapy, allogeneic NK cells, 3F8 |
Primary outcome
Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB
Time frame: 3 years
3 secondary outcomes
Estimate the anti-NB effect of allogeneic NK infusions plus 3F8
Time frame: 3 years
Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8
Time frame: 3 years
Assess the relationship between CD16 polymorphism and ADCC in vitro
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shakeel Modak, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8 in people with Neuroblastoma and Bone Marrow, Sympathetic Nervous System, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2019.