Humanized 3F8 Monoclonal Antibody (Hu3F8) When Combined With Interleukin-2 in Patients With High-Risk Neuroblastoma and GD2-positive Solid Tumors

NCT01662804 | Completed Phase 1

• 1 other identifier: 12-116
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out if "humanized 3F8" (Hu3F8) when combined with interleukin-2 (rIL2) is safe for treating neuroblastoma and other cancers. A phase 1 study means the investigators are trying to find out what side effects happen when higher and higher doses of a drug are used. The investigators want to find out what effects, good and/or bad, Hu3F8 combined with rIL2 has on cancer. The amount of Hu3F8 that patients gets will depend on when they start treatment on this study. The amount of rIL2 will be the same for all patients. The investigators also want to find out more about how Hu3F8 works and how effective it is in attacking the disease when combined with rIL2.

Conditions

Neuroblastoma

Keywords

INTERLEUKIN 2; MAB 3F8; GD2-positive tumor; 12-116

Outcome Measures

Primary Outcomes (1)

• maximum tolerated dosage

  of hu3F8 when combined with rIL-2. six dosage levels of hu3F8 will be tested with three to six patients at each dosage level.

  1 year

Secondary Outcomes (4)

• pharmacokinetics

  1 year

• anti-tumor activity

  1 year

• biologic correlates with hu3F8 dose

  1 year

• quantification of pain

  1 year

Study Arms (1)

hu3F8 and rIL-2

EXPERIMENTAL

This phase I single arm trial assesses the toxicity of escalating doses of hu3F8 (day 1 and day 8) in the presence of 6 × 10\^6 U rIL-2/m\^2/d x 5 days sc (day 8 through day 12). These 2 doses of hu3F8 and 5 doses of rIL-2 constitute a treatment cycle.

Drug: 3F8 Monoclonal Antibody Combined with Interleukin-2

Interventions

3F8 Monoclonal Antibody Combined with Interleukin-2 DRUG

One cycle has 2 days of intravenous hu3F8 treatment, given about 7 days apart. rIL-2 is administered sc daily over 5 days, beginning on the second infusion of hu3F8. To limit side-effects, patients receive analgesics and antihistamines as premedications. Cycles are 21 days. Patients can have up to 4 cycles of treatment on this study within 18 months of starting hu3F8.

hu3F8 and rIL-2

Eligibility Criteria

• Age: 13 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have either (1) a diagnosis of NB as defined by international criteria,84 i.e., histopathology (confirmed by the MSKCC Department of Pathology) or BM metastases plus high urine catecholamine levels, or (2) a tumor that is GD2-positive.
• o A non-NB tumor is defined as GD2-positive by immunostaining with m3F8. If fresh or frozen tumor is not available for immunostaining, patients will be considered eligible if published reports show that \>50% of that tumor type is GD2-positive by immunohistochemistry. (Note: Tissues must be fresh/frozen as fixed, paraffin-embedded specimens are unsuitable for anti-GD2 immunostaining). Tumors known to be GD2- positive by this criteria do not need immunostaining. These include: Melanoma (\>50%), Desmoplastic small round cell tumors (70%), Osteosarcoma (88%) and Soft tissue sarcomas including liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and spindle cell sarcoma (93%).
• Patients must have either (1) refractory or relapsed high-risk NB (including MYCN-amplified 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\*, or (2) refractory or relapsed GD2-positive tumor after receiving available life-prolonging therapies.
• \*For NB, standard therapy generally includes 5-8 cycles of high dose induction chemotherapy followed by resection of gross residual tumor, with or without myeloablative chemotherapy with peripheral blood stem cell rescue and radiation therapy to the primary site. There are also salvage chemotherapy regimens for residual disease after standard induction therapy or for relapsed NB. Some examples of these chemotherapy combinations are: high-dose cyclophosphamide, topotecan and vincristine; high-dose cyclophosphamide, irinotecan and vincristine; irinotecan and temozolomide; or ifosfamide, carboplatin and etoposide.
• Patients must be older than 1 year of age.
• Prior treatment with murine 3F8 is allowed. Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have HAHA antibody titer less than or = to 1300 Elisa units/ml
• 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.

You may not qualify if:

• 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).
• Hematologic and primary CNS malignancies
• Active life-threatening infection.
• Pregnant women or women who are breast-feeding.
• Inability to comply with protocol requirements.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neuroblastoma

Interventions

Interleukin-2

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Stephen Roberts, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 10, 2012
• Study Start: August 6, 2012
• Primary Completion: May 25, 2021
• Study Completion: May 25, 2021
• Last Updated: May 27, 2021

Record last verified: 2021-05

Locations

US (1)