Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01662804
Recruitment Status : Completed
First Posted : August 10, 2012
Last Update Posted : May 27, 2021
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Neuroblastoma Drug: 3F8 Monoclonal Antibody Combined with Interleukin-2 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) When Combined With Interleukin-2 in Patients With High-Risk Neuroblastoma and GD2-positive Solid Tumors
Actual Study Start Date : August 6, 2012
Actual Primary Completion Date : May 25, 2021
Actual Study Completion Date : May 25, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: hu3F8 and rIL-2
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
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.

Primary Outcome Measures :
  1. maximum tolerated dosage [ Time Frame: 1 year ]
    of hu3F8 when combined with rIL-2. six dosage levels of hu3F8 will be tested with three to six patients at each dosage level.

Secondary Outcome Measures :
  1. pharmacokinetics [ Time Frame: 1 year ]
    of iv hu3F8 in the presence of rIL-2. Pharmacokinetics will be measured by serial blood sampling following the first two iv doses of hu3F8. Serum hu3F8 will be measured at time 0, 5 min, 3h, 6-8h, 24h, 48h, 72h, 96, 120h and 168h after infusion for each of the two hu3F8 injections during the first cycle. Peak hu3F8 level at 5 min after infusion will also be measured for all hu3F8 infusions during all other cycles. PK analysis will be carried out by noncompartmental analysis of the serum concentration-time data using the WinNonlin software program (Pharsight Corp., Mountain View, CA).

  2. anti-tumor activity [ Time Frame: 1 year ]
    of hu3F8 plus rIL-2 against NB and other GD2-positive tumors. For neuroblastoma, anti-tumor activity will be measured by international neuroblastoma response criteria (INRC).90 For other solid tumors, the response and progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1.

  3. biologic correlates with hu3F8 dose [ Time Frame: 1 year ]
    Biologic correlate studies include (1) host immunity and (2) host WBC cytolytic capacity. The parameters measured for each patient under "host immunity" include: the induction of HAMA or HAHA, the induction of Ab3, the induction of Ab3', the induction of antibody response to tumor antigen and secondary cytokine profile.

  4. quantification of pain [ Time Frame: 1 year ]
    As patient's pain will be assessed with a numerical score of 1 to 10 over the course of the treatment, a curve of pain intensity over time can be generated for each patient. We have been collecting similar pain data for patients being treated with murine 3F8 (control group) and Hu3F8 alone and may be able use this to compare to pain data of patients receiving hu3F8 and rIL2. Because the first dose of hu3F8 will be given without rIL2 and the second dose with rIL2, we will also be able to directly compare the pain associated with hu3F8 with and without rIL2 in the same patient. This pain level will be compared to the pain scores in patients receiving m3F8 on concurrent protocols at 80 mg/m2/day or 20 mg/m2/day. Differences will be tested for significance using both Mann-Whitney and repeated measures ANOVA tests as described previously.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   13 Months and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01662804

Layout table for location information
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Layout table for investigator information
Principal Investigator: Stephen Roberts, MD Memorial Sloan Kettering Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT01662804    
Other Study ID Numbers: 12-116
First Posted: August 10, 2012    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021
Keywords provided by Memorial Sloan Kettering Cancer Center:
GD2-positive tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents