Clinical Trials /

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

Conditions

  • Neuroblastoma

Interventions

DrugSynonymsArms
Hu3F8 With GM-CSFHu3F8 with GM-CSF
Hu3F8 With GM-CSFexpansion 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

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 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.
  • Hu3F8 With GM-CSF
expansion phase II single arm trialExperimentalGroup 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.
  • Hu3F8 With GM-CSF

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 HAHA antibody titer ≤1300 Elisa
             units/ml. Human anti-mouse antibody 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.

          -  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: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:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

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

Last Updated

November 13, 2019