Clinical trial NCT01757626: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neuroblastoma
Keywords: Bone Marrow
Hu3F8
GM-CSF
12-230
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Y-mAbs Therapeutics
First posted: 2012-12-31
Enrollment: 186
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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

Primary outcomes:
measure: maximum tolerated dosage
timeFrame: 1 year
measure: assess the toxicity
timeFrame: 1 year
Secondary outcomes:
measure: pharmacokinetics of hu3F8
timeFrame: 1 year
measure: assess activity of hu3F8 plus GM-CSF against HR-NB
timeFrame: 2 years
measure: quantitate the response of marrow NB
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Brian Kushner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kushner BH, Cheung IY, Modak S, Basu EM, Roberts SS, Cheung NK. Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma: A Phase 1 Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1729-1735. doi: 10.1001/jamaoncol.2018.4005.
citation: Cheung IY, Kushner BH, Modak S, Basu EM, Roberts SS, Cheung NV. Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival. Oncoimmunology. 2017 Jul 31;6(11):e1358331. doi: 10.1080/2162402X.2017.1358331. eCollection 2017.