Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma
This study is currently recruiting participants.
Verified April 2013 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01757626
First received: December 21, 2012
Last updated: April 8, 2013
Last verified: April 2013
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Purpose
The purpose of this study is to find out if an antibody called Humanized 3F8 (Hu3F8) combined with granulocyte- macrophage colony stimulating factor (GM-CSF) is safe for treating neuroblastoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Neuroblastoma |
Biological: Hu3F8 With GM-CSF |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study of Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma |
Resource links provided by NLM:
Genetics Home Reference related topics:
neuroblastoma
Drug Information available for:
Sargramostim
U.S. FDA Resources
Further study details as provided by Memorial Sloan-Kettering Cancer Center:
Primary Outcome Measures:
- maximum tolerated dosage [ Time Frame: 1 year ] [ Designated as safety issue: No ]hu3F8 when combined with GM-CSF. DLT is defined after 1 cycle. Four dosage levels of hu3F8 will be tested with three to six patients at each dosage level.
- assess the toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]of the humanized anti GD2 antibody hu3F8 when combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in patients with high risk neuroblastoma. All observed adverse events, regardless of treatment group or suspected causal relationship to study drug will be recorded. Adverse events will be identified and graded using the Common Toxicity Criteria Version 4.0
Secondary Outcome Measures:
- pharmacokinetics of hu3F8 [ Time Frame: 1 year ] [ Designated as safety issue: No ]when combined with GM-CSF. Pharmacokinetics will be measured by serial blood sampling following the first two iv doses of hu3F8 as listed in Table 3. Serum hu3F8 will be measured pre-infusion and at time pre- (within an hour before hu3F8), 5 min, 3h, 6-8h, 24h, 48h, 72h, 96, 120h, 168h 216h and 264h after the first infusion of hu3F8 during cycle1 and, whenever possible, peak hu3F8 level at ~30 minutes pre- and ~5 mopntues post-infusion will also be measured for each dose of hu3F8 in cycles 2, 3 and 4.
- assess activity of hu3F8 plus GM-CSF against NB [ Time Frame: 1 year ] [ Designated as safety issue: No ]Another secondary objective is to assess the anti-tumor activity of hu3F8 against NB and other GD2-positive tumors. Anti-tumor activity will be measured by international neuroblastoma response criteria (INRC).
- quantitate the response of marrow NB [ Time Frame: 1 year ] [ Designated as safety issue: No ]will be measured using quantitative Reverse transcription-PCR (qRTPCR) and its relationship with dosage of hu3F8 explored.
| Estimated Enrollment: | 24 |
| Study Start Date: | December 2012 |
| Estimated Study Completion Date: | December 2014 |
| Estimated Primary Completion Date: | December 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Hu3F8 with GM-CSF
This phase I single arm trial assesses escalating doses of iv hu3F8 (days 1, 3, 5) in the presence of sc GM-CSF (day -4 through 5).
|
Biological: Hu3F8 With GM-CSF
Once cycle consists of treatment with hu3F8 for 3 days (day 1, 3 and 5). GM-CSF is started 5 days in advance of each hu3F8 cycle at 250 mcg/m2/day (day -4 to day 0), and at 500 mcg/m2/day x 5 days (day 1 to day 5). Cycles are 5 days. Cycles are repeated at 2-4 week intervals between first days of hu3F8, through 4 cycles.
|
Eligibility| Ages Eligible for Study: | 1 Year and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of NB as defined by a) histopathology (confirmed by the MSKCC Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
Patients must have either refractory or relapsed high-risk NB (including MYCNamplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age) resistant to standard therapy*.
*For NB, standard therapy includes intensive induction chemotherapy, followed by a variety of consolidation or salvage therapies, depending on response.
- Patients must be older than 1 year of age.
- Prior treatment with murine and humanized 3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have HAHA antibody titer ≤1300 Elisa units/ml. Human anti-mouse antibody positivity is allowed.
- White blood cell count ≥1000/ul
- Absolute neutrophil count ≥500/ul
- Absolute lymphocyte count ≥500/ul
- Platelet count ≥25,000/ul
- No chemotherapy or immunotherapy for a minimum of three weeks prior to study enrollment
- Women of child-bearing potential must be willing to practice an effective method of birth control while on treatment
- Signed informed consent indicating awareness of the investigational nature of this program.
Exclusion Criteria:
- Existing major organ dysfunction > grade 2, with the exception of hearing loss and hematologic toxicity (defined as suppression of all subtypes of WBCs, RBCs, and platelets).
- Active life-threatening infection.
- Pregnant women or women who are breast-feeding.
- Inability to comply with protocol requirements, including PK studies and genetic studies.
- History of allergy to mouse proteins.
- Human anti-hu3F8 antibody (HAHA) titer >1300 Elisa units/ml.
- History of allergy to GM-CSF
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01757626
Contacts
| Contact: Brian Kushner, MD | 212-639-6793 | |
| Contact: Nai-Kong Cheung, MD, PhD | 646-888-2313 |
Locations
| United States, New York | |
| Memorial Sloan-Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: Brian Kushner, MD 212-639-6793 | |
| Contact: Nai-Kong Cheung, MD, PhD 646-888-2313 | |
| Principal Investigator: Brian Kushner, MD | |
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
| Principal Investigator: | Brian Kushner, MD | Memorial Sloan-Kettering Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Memorial Sloan-Kettering Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01757626 History of Changes |
| Other Study ID Numbers: | 12-230 |
| Study First Received: | December 21, 2012 |
| Last Updated: | April 8, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Memorial Sloan-Kettering Cancer Center:
|
Bone Marrow Hu3F8 GM-CSF 12-230 |
Additional relevant MeSH terms:
|
Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
ClinicalTrials.gov processed this record on May 22, 2013