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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Neuroblastoma

Treatments: Biological: Hu3F8 With GM-CSF

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01757626

12-230

Details and patient eligibility

About

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.

Enrollment: 186 patients

Sex: All

Ages: 1+ year old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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186 participants in 2 patient groups

Hu3F8 with GM-CSF

Experimental group

Description:

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.

Treatment:

Biological: Hu3F8 With GM-CSF

Biological: Hu3F8 With GM-CSF

expansion phase II single arm trial

Experimental group

Description:

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.

Treatment:

Biological: Hu3F8 With GM-CSF

Biological: Hu3F8 With GM-CSF