Trial record 1 of 1 for:
NCT00381680
Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia
This study is currently recruiting participants.
Verified May 2013 by Children's Oncology Group
Sponsor:
Children's Oncology Group
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00381680
First received: September 26, 2006
Last updated: May 15, 2013
Last verified: May 2013
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Purpose
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways and different doses may kill more cancer cells. It is not yet known whether low-dose vincristine is more effective than high-dose vincristine (closed to accrual as of 09/2010) when given together with different combination chemotherapy regimens in treating acute lymphoblastic leukemia.
PURPOSE: This randomized phase III trial is studying low-dose vincristine to see how well it works compared with high-dose vincristine(closed to accrual as of 09/2010) when given together with different combination chemotherapy regimens in treating young patients with intermediate-risk relapsed B-cell acute lymphoblastic leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Biological: filgrastim Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide phosphate Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: pegaspargase Drug: prednisone Drug: therapeutic hydrocortisone Drug: vincristine sulfate Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Intensive Treatment for Intermediate-Risk Relapse of Childhood B-Precursor Acute Lymphoblastic Leukemia (ALL): A Randomized Trial of Vincristine Strategies |
Resource links provided by NLM:
Drug Information available for:
Dexamethasone
Hydrocortisone acetate
Cyclophosphamide
Hydrocortisone
Mercaptopurine
Prednisone
Methotrexate
Folic acid
Hydrocortisone sodium succinate
Cytarabine
Calcium Gluconate
Hydrocortisone cypionate
Dexamethasone acetate
Leucovorin calcium
Vincristine sulfate
Dexamethasone sodium phosphate
Asparaginase
Hydrocortisone butyrate
Sulfate ion
Methotrexate sodium
Doxorubicin
Doxorubicin hydrochloride
Etoposide
Hydrocortisone valerate
Levoleucovorin
Hydrocortisone probutate
Etoposide phosphate
Filgrastim
Pegaspargase
Lenograstim
Granulocyte colony-stimulating factor
U.S. FDA Resources
Further study details as provided by Children's Oncology Group:
Primary Outcome Measures:
- Efficacy of therapy [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]Efficacy of therapy of an intensive chemotherapy regimen. (based on POG 9412) for patients with intermediate-risk relapse of childhood B-precursor ALL. Power calculations are based on the assumption of proportional hazards, and using the log rank test (alpha=0.1, one-sided test). The efficacy stopping boundaries to be used will be based on the alpha x (time)^2 spending function. The study will also be monitored for futility. The lower boundaries are based on testing the alternative hypothesis at the 0.005 level.
- Event-free survival at 3 years [ Time Frame: At 3 years ] [ Designated as safety issue: No ]A 95% confidence interval will be constructed using data on the standard dosing VCR arm at the time of study completion. If the lower bound of the confidence interval is larger than 40%, then the intensified chemotherapy will be deemed as efficacious. correlation between MRD and EFS will be essentially descriptive.
Secondary Outcome Measures:
- Frequency and severity of adverse effects assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 107 weeks ] [ Designated as safety issue: Yes ]If 7 or more of the first 30 patients (combined in both arms) experience Grade 3 peripheral neurotoxicity then the accrual of adolescents will be temporarily closed. A one-sided Z-test for testing the equality of proportions with alpha=0.05 and with early stopping boundaries based on the t1/2 alpha spending function will be used. Osteonecrosis will be closely monitored on this study - overall and among patients less than ten years and those greater than or equal to ten years of age at the time of enrollment on study.
- Gene expression profile of early versus late marrow relapse by DNA microarray [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]Genes predictive of outcome will be identified using statistical methods and multiple supervised machine learning algorithms with rigorous cross validation. Profiles will be correlated with time of relapse (early vs. late). Expression profiles derived from relapse samples will be compared to the gene expression classifiers derived from pretreatment samples. Three-year EFS for these two groups varies from less than 20% for early marrow relapse to 40% - 50% for late relapse
| Estimated Enrollment: | 418 |
| Study Start Date: | March 2007 |
| Estimated Primary Completion Date: | March 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm I (low-dose vincristine and combination chemotherapy)
Pts receive cranial radiation therapy. Induction of low-dose vincristine sulfate in combo chemotherapy (etoposide phosphate, prednisone, doxorubicin hydrochloride, pegaspargase, cytarabine, methotrexate) on wks 1-5. CNS+ pts receive (ITT-methotrexate, therapeutic hydrocortisone, cytarabine). They also receive additional induction (etoposide phosphate, cyclophosphamide, methotrexate, leucovorin calcium, cytarabine, asparaginase and filgrastim) on wks 6-10 & 11-15, an intensified regimen (vincristine, methotrexate, leucovorin calcium, mercaptopurine, etoposide phosphate, cyclophosphamide) on wks 16-7, re-induction regimen on wks 28-32 (vincristine,doxorubicin,dexamethasone,pegaspargase, methotrexate), intensified regimen on wks 33-56 (cytarabine, pegaspargase, vincristine sulfate, methotrexate, leucovorin calcium,mercaptopurine,etoposide and cyclophosphamide), a maintenance regimen on wks 57-106 (methotrexate, mercaptopurine, dexamethasone, vincristine, cyclophosphamide).
|
Biological: filgrastim
Given IV, subcutaneously
Other Names:
Drug: asparaginase
Given IM
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cytarabine
Given IV, intrathecally
Other Names:
Drug: dexamethasone
Given orally
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: etoposide phosphate
Given IV
Other Names:
Drug: leucovorin calcium
Given IV or orally
Other Names:
Drug: mercaptopurine
Given orally
Other Names:
Drug: methotrexate
Given orally, intrathecally
Other Names:
Drug: pegaspargase
Given IM
Other Names:
Drug: prednisone
Given orally 3 times daily
Other Names:
Drug: therapeutic hydrocortisone
Given intrathecally
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Radiation: radiation therapy
Beginning in week 1 of the first maintenance therapy course, patients with CNS relapse undergo cranial radiotherapy once daily, 5 days a week, for 10 days.
|
|
Experimental: Arm II (high-dose vincristine and combination chemotherapy)
Patients receive induction therapy comprising high-dose vincristine sulfate in combination with chemotherapy on weeks 1-5. They also receive additional induction therapy on weeks 6-10 and 11-15, an intensified chemotherapy regimen on weeks 16-7, a re-induction regimen on weeks 28-32, an intensified regimen on weeks 33-56, and a maintenance regimen on weeks 57-106.(closed to accrual as of 09/2010).
|
Biological: filgrastim
Given IV, subcutaneously
Other Names:
Drug: asparaginase
Given IM
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cytarabine
Given IV, intrathecally
Other Names:
Drug: dexamethasone
Given orally
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: etoposide phosphate
Given IV
Other Names:
Drug: leucovorin calcium
Given IV or orally
Other Names:
Drug: mercaptopurine
Given orally
Other Names:
Drug: methotrexate
Given orally, intrathecally
Other Names:
Drug: pegaspargase
Given IM
Other Names:
Drug: prednisone
Given orally 3 times daily
Other Names:
Drug: therapeutic hydrocortisone
Given intrathecally
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Radiation: radiation therapy
Beginning in week 1 of the first maintenance therapy course, patients with CNS relapse undergo cranial radiotherapy once daily, 5 days a week, for 10 days.
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 1 Year to 29 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Diagnosis of acute lymphoblastic leukemia (ALL)
Bone marrow with > 25% L1 or L2 lymphoblasts (M3 marrow)
- Patients with > 25% L3 marrow lymphoblasts and/or evidence of c-myc translocation are not eligible (considered Burkitt's or mature B-cell leukemia)
Intermediate-risk relapsed disease, meeting 1 of the following criteria:
- Bone marrow relapse ≥ 36 months after initial diagnosis (defined as M3 marrow after previous remission from ALL)
- Combined bone marrow and extramedullary (CNS* and/or testicular**) relapse ≥ 36 months after initial diagnosis
- Isolated extramedullary (CNS* and/or testicular**) relapse < 18 months after initial diagnosis NOTE: *CNS relapse is defined as WBC ≥ 5/mm³ in cerebral spinal fluid (CSF) with blasts present on cytospin OR any number of WBC in CSF with immunophenotypic proof of leukemic relapse (defined as identifiable blasts plus [for B-lineage] TdT or CD-10 positivity on 2 consecutive CSF samples obtained 4 weeks apart)
NOTE: **Testicular relapse is defined as unilateral or bilateral testiculomegaly with biopsy-proven testicular involvement OR unilateral or bilateral testiculomegaly with concurrent relapse in the bone marrow and/or CNS
The following subtypes are not allowed:
- T-lineage ALL
- Mature B-cell (Burkitt's) leukemia (defined as L3 morphology and/or evidence of c-myc translocation)
- Philadelphia-chromosome positive disease
- No Down syndrome (trisomy 21)
PATIENT CHARACTERISTICS:
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
- Bilirubin < 3.0 mg/dL
- Not pregnant
- Fertile patients must use effective contraception
- No history of peripheral neuropathy ≥ grade 3 within the past month
- No toxicity (i.e. peripheral neuropathy) ≥ grade 3 attributable to vincristine within the past month
PRIOR CONCURRENT THERAPY:
- At least 5 days since prior intrathecal chemotherapy
- No prior hematopoietic stem cell or marrow transplantation
- No prior cranial radiotherapy > 1200 cGy (for patients with CNS relapse)
- No concurrent stem cell transplant
- No concurrent alternative therapy
- No concurrent itraconazole in patients receiving vincristine
- No concurrent intensity-modulated radiotherapy
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00381680
Show 167 Study Locations
Show 167 Study LocationsSponsors and Collaborators
Children's Oncology Group
Investigators
| Study Chair: | Glen Lew, MD | AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus |
| Study Chair: | Rochelle A. Yanofsky, MD | CancerCare Manitoba |
More Information
Additional Information:
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00381680 History of Changes |
| Other Study ID Numbers: | AALL0433, COG-AALL0433, CDR0000495359 |
| Study First Received: | September 26, 2006 |
| Last Updated: | May 15, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Children's Oncology Group:
|
B-cell childhood acute lymphoblastic leukemia recurrent childhood acute lymphoblastic leukemia L1 childhood acute lymphoblastic leukemia L2 childhood acute lymphoblastic leukemia |
Additional relevant MeSH terms:
|
Burkitt Lymphoma Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases Tumor Virus Infections Lymphoma, Non-Hodgkin Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoma, B-Cell Neoplasms, Experimental |
Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases 6-Mercaptopurine Cytarabine Methotrexate Cyclophosphamide Etoposide phosphate Pegaspargase Asparaginase Dexamethasone Doxorubicin Etoposide Prednisone |
ClinicalTrials.gov processed this record on May 23, 2013