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131I-MIBG Alone VS. 131I-MIBG With Vincristine and Irinotecan VS131I-MIBG With Vorinostat

Phase 2
Completed
Conditions
Neuroblastoma
Interventions
Registration Number
NCT02035137
Lead Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Brief Summary

This study will compare three treatment regimens containing metaiodobenzylguanidine (MIBG) and compare their effects on tumor response and associated side effects, to determine if one therapy is better than the other for people diagnosed with relapsed or persistent neuroblastoma.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
114
Inclusion Criteria
  • Patients must be > 24 months and < 30 years of age when registered on study.
  • Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to frontline therapy frontline therapy with > 3 residual lesions on end-induction MIBG scan.
  • Patients must have evidence of MIBG uptake into tumor at ≥ one site within 4 weeks prior to entry on study and subsequent to any intervening therapy.
  • Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
  • Patients must have a dose of unpurged peripheral blood stem cells is 2.0 x 106 viable CD34+ cells/kg available.
Exclusion Criteria
  • They have had previous I-131 MIBG therapy
  • They have other medical problems that could get much worse with this treatment.
  • They are pregnant or breast feeding.
  • They have a history of a venous or arterial thrombosis that was not associated to a central line.
  • They have active infections such as hepatitis or fungal infections.
  • They have active diarrhea.
  • They have had an allogeneic stem cell transplant (received stem cell from someone else)
  • They can't cooperate with the special precautions that are needed for this trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
131I-MIBG with Vincristine/Irinotecan131I-MIBGVincristine / irinotecan / 131I-MIBG (Arm B): vincristine 2 mg/m2 (maximum dose 2 mg) intravenously on Day 0; irinotecan 50 mg/m2 (maximum dose 100 mg) intravenously on Days 0 to 4. Patients will also receive diarrhea prophylaxis with cefixime 8 mg/kg/day orally on Days -1 to +6. 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.
131I-MIBG with Vorinostat131I-MIBGVorinostat / 131I-MIBG (Arm C); vorinostat 180 mg/m2 (maximum dose 400 mg) orally once daily on Days -1 to +12 (14 total doses). 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.
Single-Agent 131I-MIBG131I-MIBGSingle-agent 131I-MIBG (Arm A) 18 mCi/kg 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15.
131I-MIBG with Vincristine/IrinotecanVincristineVincristine / irinotecan / 131I-MIBG (Arm B): vincristine 2 mg/m2 (maximum dose 2 mg) intravenously on Day 0; irinotecan 50 mg/m2 (maximum dose 100 mg) intravenously on Days 0 to 4. Patients will also receive diarrhea prophylaxis with cefixime 8 mg/kg/day orally on Days -1 to +6. 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.
131I-MIBG with VorinostatVorinostatVorinostat / 131I-MIBG (Arm C); vorinostat 180 mg/m2 (maximum dose 400 mg) orally once daily on Days -1 to +12 (14 total doses). 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.
131I-MIBG with Vincristine/IrinotecanIrinotecanVincristine / irinotecan / 131I-MIBG (Arm B): vincristine 2 mg/m2 (maximum dose 2 mg) intravenously on Day 0; irinotecan 50 mg/m2 (maximum dose 100 mg) intravenously on Days 0 to 4. Patients will also receive diarrhea prophylaxis with cefixime 8 mg/kg/day orally on Days -1 to +6. 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.
Primary Outcome Measures
NameTimeMethod
Objective Tumor Response After One Course of Therapy43-50 days from study day 1

To identify the MIBG treatment regimen associated with the highest overall response rate after one course of treatment on the three arms. The response evaluation was based on central review (intent to treat analysis). Responders defined as meeting CR/MRD/PR criteria. Response was based on NANT response criteria v1.2 (https://doi.org/10.1002/pbc.26940). RECST 1.1 criteria was used for measurable tumors with PR criteria \> 30% decrease in target tumor size. Curie score was used with PR criteria \> 50% decrease in Curie score. Complete Response- disappearance of all target lesions, Curie score of 0 and no detectable bone marrow disease. Overall Response (OR)=CR+PR.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Grade 3 or Greater Non-hematologic ToxicitiesAll toxicities from enrollment through 30 days following end of protocol therapy, an average of 6 months

Compare toxicity profiles for grade 3 or greater toxicities associated with each of 131I-MIBG treatment regimens; single-agent 131I-MIBG; Vincristine/Irinotecan/131I-MIBG; or Vorinostat/131I-MIBG

Trial Locations

Locations (14)

Children Hospital of Colorado

🇺🇸

Aurora, Colorado, United States

Children's Hospital Boston

🇺🇸

Boston, Massachusetts, United States

University of North Carolina

🇺🇸

Chapel Hill, North Carolina, United States

Childrens Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

🇺🇸

Atlanta, Georgia, United States

Cincinnati Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

Lucile Salter Packer Children's Hospital

🇺🇸

Palo Alto, California, United States

University of Chicago, Comer Children's Hospital

🇺🇸

Chicago, Illinois, United States

C.S Mott Children's Hospital

🇺🇸

Ann Arbor, Michigan, United States

Cook Children's Healthcare System

🇺🇸

Fort Worth, Texas, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

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