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Combination Therapy of Antibody Hu3F8 With Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) in Patients With Relapsed/Refractory High-Risk Neuroblastoma

NCT01757626

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.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

Trial Conditions

  • Neuroblastoma

Trial Interventions

DrugSynonymsArms

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Hu3F8 with GM-CSFExperimentalThe 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/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 123I-MIBG scan.

    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 update in osteomedullary sites, OR 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 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 (phase I only)

    - Platelet count ≥25,000/ul

    - 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.

    - Human anti-hu3F8 antibody (HAHA) titer >1300 Elisa units/ml.

    - History of allergy to GM-CSF

    Maximum Eligible Age:N/A
    Minimum Eligible Age:1 Year
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:maximum tolerated dosage
    Time Frame:1 year
    Safety Issue:No
    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:No
    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 NB
    Time Frame:1 year
    Safety Issue:No
    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:No
    Description:will be measured using quantitative Reverse transcription-PCR (qRTPCR) and its relationship with dosage of hu3F8 explored.

    Trial Keywords

    • Bone Marrow
    • Hu3F8
    • GM-CSF
    • 12-230