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. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01757626
First received: December 21, 2012
Last updated: June 24, 2014
Last verified: June 2014
  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:


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. Nine 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 pre- and ~5 minutes post-infusion will also be measured for each dose of hu3F8 in subsequent cycles .

  • 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 2015
Estimated Primary Completion Date: December 2015 (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. Patients who complete 4 cycles of treatment without complications or disease progression have the option of continuing treatment for up to 24 months from their first dose of hu3F8.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: June 24, 2014
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
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral

ClinicalTrials.gov processed this record on October 22, 2014