Description:
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.
Title
- Brief Title: Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma
- Official Title: Phase I/II Study of Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma
Clinical Trial IDs
- ORG STUDY ID:
12-230
- NCT ID:
NCT01757626
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Hu3F8 With GM-CSF | | Hu3F8 with GM-CSF |
| Hu3F8 With GM-CSF | | expansion phase II single arm trial |
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Hu3F8 with GM-CSF | Experimental | The 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). These 3 doses of hu3F8 and 10 days of GM-CSF constitute a treatment cycle. The expansion phase II single arm trial assesses the anti-NB activity of hu3F8+GM-CSF.in 3 groups of patients: Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123I-MIBG scan. Group 2 patients are in ≥2nd CR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123I-MIBG scan. Ph II: Groups 1 & 3 pts can continue to get cycles every 1-2 months for up to 24 months from study enrollment or until they receive 5 cycles after a major response (CR or PR) is achieved. | |
| expansion phase II single arm trial | Experimental | Group 1 patients have primary refractory disease (no prior relapse but incomplete response to treatment) in BM as documented by histology and/or 123^I-MIBG scan. Group 2 patients are in >2nd CR/VGPR and at high risk for another relapse. Group 3 patients have secondary refractory disease (prior relapse and incomplete response to retrieval therapy) in BM as documented by histology and/or 123^I-MIBG scan. GM-CSF can be omitted if patients have a history of an allergy to GM-CSF or develop an allergic reaction to GM-CSF after initiating therapy while on the protocol. | |
Eligibility 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 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) AND:
- Phase I: Patients must have refractory or relapsed NB, resistant to standard therapy*.
*For NB, standard therapy includes intensive induction chemotherapy, followed by a
variety of consolidation or salvage therapies, depending on response.
- Phase II: Patients must have primary or secondary refractory disease in BM, defined as
morphologic evidence of NB in BM and/or abnormal 123I-MIBG uptake in osteomedullary
sites, OR patients patients in ≥ 2nd CR patients are in ≥2nd CR
- 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 a negative HAHA antibody titer. Human
anti-mouse antibody (HAMA) positivity is allowed.
- White blood cell count ≥1000/ul (phase I only)
- Absolute neutrophil count ≥500/ul (phase I only)
- Absolute lymphocyte count ≥500/ul (phase I only)
- Platelet count ≥25,000/ul (phase I only)
- No chemotherapy or immunotherapy for a minimum of three weeks prior to start of hu3F8
- 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 (phase I only)
- History of allergy to mouse proteins.
- Positive human anti-hu3F8 antibody (HAHA) titer
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 1 Year |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | maximum tolerated dosage |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | hu3F8 when combined with GM-CSF. DLT is defined after 1 cycle. Seventeen dosage levels of hu3F8 will be tested with three to six patients at each dosage level. |
Secondary Outcome Measures
| Measure: | pharmacokinetics of hu3F8 |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | (Phase I) 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 pre- and ~5 minutes post-infusion will also be measured for each dose of hu3F8 in subsequent cycles . |
| Measure: | assess activity of hu3F8 plus GM-CSF against HR-NB |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | 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). |
| Measure: | quantitate the response of marrow NB |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | will be measured using quantitative Reverse transcription-PCR (qRTPCR) and its relationship with dosage of hu3F8 explored. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
Trial Keywords
- Bone Marrow
- Hu3F8
- GM-CSF
- 12-230
Last Updated
May 3, 2021
