Study Stopped
Administratively complete.
Pyrazoloacridine and Stem Cell or Bone Marrow Transplantation in Treating Young Patients With High-Risk Neuroblastoma
A Phase I Study of High-dose Pyrazoloacridine (PZA) (NSC 366140) Supported With Autologous Hematopoietic Stem Cell Rescue in Children With Recurrent or Resistant Neuroblastoma (IND # 36325)
5 other identifiers
interventional
42
1 country
1
Brief Summary
This phase I trial is studying the side effects and best dose of pyrazoloacridine given together with peripheral stem cell or bone marrow transplantation in treating young patients with high-risk neuroblastoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2002
CompletedFirst Submitted
Initial submission to the registry
February 5, 2003
CompletedFirst Posted
Study publicly available on registry
February 6, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2007
CompletedApril 9, 2013
April 1, 2013
4.2 years
February 5, 2003
April 8, 2013
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum tolerated dose determined by dose-limiting toxicities by NCI Common Toxicity Criteria
28 days
Secondary Outcomes (6)
Time to engraftment (hematopoietic recovery)
Up to 4 years
Response by RECIST or MIBG-scans
28 days
Survival
Up to 4 years
Time to progression
Up to 4 years
Time to failure
Time from start of treatment until death for any cause or disease progression, assessed up to 4 years
- +1 more secondary outcomes
Study Arms (2)
Cohort I
EXPERIMENTALGroups of 3-6 patients receive escalating doses of PZA at a fixed infusion time until the MTD is determined. In both cohorts the MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients receive G-CSF IV or subcutaneously beginning on day 4 and continuing until blood counts recover. Patients also undergo reinfusion of stem cells over 15-30 minutes on day 4 as needed per protocol.
Cohort II
EXPERIMENTALGroups of 3-6 patients receive PZA at the dose/hour established in cohort I at escalating infusion times until another MTD is determined. In both cohorts the MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients receive G-CSF IV or subcutaneously beginning on day 4 and continuing until blood counts recover. Patients also undergo reinfusion of stem cells over 15-30 minutes on day 4 as needed per protocol.
Interventions
Undergo autologous bone marrow transplantation
Undergo peripheral blood stem cell transplantation
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have a diagnosis of neuroblastoma (ICD-O morphology 9500/3) verified by histology and/or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites
- Patients must meet one of the two following disease status criteria to enter on study;
- Current or prior progressive disease (PD) by INRC criteria
- Either mixed response (MR) or no response (NR) by INRC criteria following completion of minimum of 4 courses of induction therapy
- Patients meeting disease status criteria in either category A or B must also have at least one of the following sites of disease present to enter on study:
- At least one tumor lesion on CT or MRI scan that is \>= 20mm in at least one dimension (spiral CT lesion must be \>= 10mm in at least one dimension)
- MIBG scan with positive uptake at a minimum of one site
- Bone marrow disease documented by standard histology of bilateral bone marrow aspirate and biopsy specimens
- Patients \> 16 years of age: Karnofsky \>= 50%; Patients =\< 16 years of age: Lansky \>= 50%; patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score; life expectancy must be \>= 2 months for all patients
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Chemotherapy and/or biologics: Must not have received treatment within 3 weeks of entry onto this study (4 weeks if prior nitrosureas
- Radiation: At least 4 weeks since last dose of radiation therapy to at least one lesion being used as criteria for study eligibility; only 2 weeks must elapse since the last dose of radiation (small port) to a lesion not used for study eligibility; at least 6 months must have elapsed since the last dose of prior craniospinal XRT and radiation to \>= 50% of the pelvis or TBI
- Stem Cell Transplant (SCT): \>= 9 months must have elapsed since autologous hematopoietic stem cell transplant (aHSCT)
- Prior MIBG therapy: At least 12 weeks must have elapsed since treatment with therapeutic doses of MIBG
- Study specific limitations on prior therapy: patients who have a history of allogeneic HSCT are not eligible
- +12 more criteria
You may not qualify if:
- No patients who are pregnant or lactating will be allowed to enter on study; pregnancy tests must be obtained in females who are post-menarchal; males and females of reproductive potential may not participate unless they have agreed to use an effective method of contraception while receiving therapy
- Patients with active infections requiring intravenous antivirals, antibiotics, or antifungals; patients on prolonged antifungal therapy are still eligible if they are culture negative and biopsy negative in suspected residual radiographic lesions and they meet other organ function criteria; patients who are known HIV seropositive with stable disease and lack of major health problems who are not on anti-retroviral therapy, may be eligible at the discretion of the Study Chair
- Prior treatment with Pyrazoloacridine (PZA)
- Prior history of allogeneic HSCT
- Acute or chronic CNS disease
- History of seizures
- History of cerebral bleeding or stroke
- CNS parenchymal metastases as documented by head CT with contrast or head MRI with gadolinium performed within 30 days of study entry. Patients with epidural metastases causing mass effect on the brain are also excluded (skull metastases are allowed provided they are not associated with intracranial disease compressing or displacing the brain
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
New Approaches to Neuroblastoma Treatment (NANT)
Los Angeles, California, 90027-6016, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Anna Butturini
New Approaches to Neuroblastoma Treatment (NANT)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 5, 2003
First Posted
February 6, 2003
Study Start
December 1, 2002
Primary Completion
March 1, 2007
Last Updated
April 9, 2013
Record last verified: 2013-04