Neuroblastoma
Conditions
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.
Interventions
Sponsors
New Approaches to Neuroblastoma Therapy Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 30 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response After One Course of Therapy | 43-50 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Greater Non-hematologic Toxicities | All 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 |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single-Agent 131I-MIBG Single-agent 131I-MIBG (Arm A) 18 mCi/kg 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15.
131I-MIBG | 38 |
| 131I-MIBG With Vincristine/Irinotecan Vincristine / 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. 31I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.
131I-MIBG
Vincristine
Irinotecan | 36 |
| 131I-MIBG With Vorinostat Vorinostat / 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
Vorinostat | 37 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Disease progression prior to treatment start | 2 | 0 | 0 |
| Overall Study | Ineligible | 0 | 1 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | 131I-MIBG With Vorinostat | Total | 131I-MIBG With Vincristine/Irinotecan | Single-Agent 131I-MIBG |
|---|---|---|---|---|
| Age, Categorical <=18 years | 36 Participants | 107 Participants | 34 Participants | 37 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 24 Participants | 7 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 82 Participants | 27 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 6 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 12 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 16 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 23 Participants | 72 Participants | 23 Participants | 26 Participants |
| Region of Enrollment Canada | 1 participants | 3 participants | 1 participants | 1 participants |
| Region of Enrollment United States | 36 participants | 108 participants | 35 participants | 37 participants |
| Sex: Female, Male Female | 16 Participants | 52 Participants | 17 Participants | 19 Participants |
| Sex: Female, Male Male | 21 Participants | 59 Participants | 19 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 11 / 38 | 17 / 36 | 18 / 37 |
| other Total, other adverse events | 37 / 38 | 35 / 36 | 35 / 37 |
| serious Total, serious adverse events | 6 / 38 | 12 / 36 | 5 / 37 |
Outcome results
Primary
Objective Tumor Response After One Course of Therapy
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.
Time frame: 43-50 days from study day 1
Population: Number of eligible randomized patients who received 131-I-MIBG therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-Agent 131I-MIBG | Objective Tumor Response After One Course of Therapy | 5 Participants |
| 131I-MIBG With Vincristine/Irinotecan | Objective Tumor Response After One Course of Therapy | 5 Participants |
| 131I-MIBG With Vorinostat | Objective Tumor Response After One Course of Therapy | 11 Participants |
Secondary
Number of Participants With Grade 3 or Greater Non-hematologic Toxicities
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
Time frame: All toxicities from enrollment through 30 days following end of protocol therapy, an average of 6 months
Population: Patients who were eligible, randomized, and received 131I-MIBG treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-Agent 131I-MIBG | Number of Participants With Grade 3 or Greater Non-hematologic Toxicities | 7 Participants |
| 131I-MIBG With Vincristine/Irinotecan | Number of Participants With Grade 3 or Greater Non-hematologic Toxicities | 17 Participants |
| 131I-MIBG With Vorinostat | Number of Participants With Grade 3 or Greater Non-hematologic Toxicities | 12 Participants |