Low-Dose or High-Dose Vincristine and Combination Chemotherapy in Treating Young Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia - Full Text View

Sponsors and Collaborators:	Children's Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00381680

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 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 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	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide phosphate Drug: filgrastim Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: pegaspargase Drug: prednisone Drug: therapeutic hydrocortisone Drug: vincristine sulfate Procedure: radiation therapy	Phase III

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Filgrastim Cytarabine Cytarabine hydrochloride Etoposide Mercaptopurine 6-Mercaptopurine L-Asparaginase Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Hydrocortisone Cortisol 21-phosphate Cortisol succinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone acetate Hydrocortisone cypionate Hydrocortisone hemisuccinate Proctofoam-HC Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Prednisone Vincristine sulfate Vincristine Etoposide phosphate Calcium gluconate Pegaspargase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	Intensive Treatment for Intermediate-Risk Relapse of Childhood B-Precursor Acute Lymphoblastic Leukemia (ALL): A Randomized Trial of Vincristine Strategies

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Efficacy of therapy [ Designated as safety issue: No ]
Event-free survival at 3 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Frequency and severity of adverse effects at 3 years [ Designated as safety issue: Yes ]

Estimated Enrollment:	418
Study Start Date:	March 2007
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients will receive infusions of low-dose vincristine as part of their combination chemotherapy regimen. They will receive combination chemotherapy by mouth, injection, and infusion and intrathecally for up to approximately 2 years. They will also receive injections of G-CSF.	Drug: asparaginase Given IM Drug: cyclophosphamide Given IV Drug: cytarabine Given IV, intrathecally Drug: dexamethasone Given orally Drug: doxorubicin hydrochloride Given IV Drug: etoposide phosphate Given IV Drug: filgrastim Given IV, subcutaneously Drug: leucovorin calcium Given IV or orally Drug: mercaptopurine Given orally Drug: methotrexate Given orally, intrathecally Drug: pegaspargase Given IM Drug: prednisone Given orally Drug: therapeutic hydrocortisone Given intrathecally Drug: vincristine sulfate Given IV Procedure: 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.
Arm II: Experimental Patients will receive infusions of high-dose vincristine as part of their combination chemotherapy regimen. They will receive combination chemotherapy by mouth, injection, and infusion and intrathecally for up to approximately 2 years. They will also receive injections of G-CSF.	Drug: asparaginase Given IM Drug: cyclophosphamide Given IV Drug: cytarabine Given IV, intrathecally Drug: dexamethasone Given orally Drug: doxorubicin hydrochloride Given IV Drug: etoposide phosphate Given IV Drug: filgrastim Given IV, subcutaneously Drug: leucovorin calcium Given IV or orally Drug: mercaptopurine Given orally Drug: methotrexate Given orally, intrathecally Drug: pegaspargase Given IM Drug: prednisone Given orally Drug: therapeutic hydrocortisone Given intrathecally Drug: vincristine sulfate Given IV Procedure: 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.

Arms

Assigned Interventions

Arm I: Active Comparator

Patients will receive infusions of low-dose vincristine as part of their combination chemotherapy regimen. They will receive combination chemotherapy by mouth, injection, and infusion and intrathecally for up to approximately 2 years. They will also receive injections of G-CSF.

Drug: asparaginase

Given IM

Drug: cyclophosphamide

Given IV

Drug: cytarabine

Given IV, intrathecally

Drug: dexamethasone

Given orally

Drug: doxorubicin hydrochloride

Given IV

Drug: etoposide phosphate

Given IV

Drug: filgrastim

Given IV, subcutaneously

Drug: leucovorin calcium

Given IV or orally

Drug: mercaptopurine

Given orally

Drug: methotrexate

Given orally, intrathecally

Drug: pegaspargase

Given IM

Drug: prednisone

Given orally

Drug: therapeutic hydrocortisone

Given intrathecally

Drug: vincristine sulfate

Given IV

Procedure: 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.

Arm II: Experimental

Patients will receive infusions of high-dose vincristine as part of their combination chemotherapy regimen. They will receive combination chemotherapy by mouth, injection, and infusion and intrathecally for up to approximately 2 years. They will also receive injections of G-CSF.

Drug: asparaginase

Given IM

Drug: cyclophosphamide

Given IV

Drug: cytarabine

Given IV, intrathecally

Drug: dexamethasone

Given orally

Drug: doxorubicin hydrochloride

Given IV

Drug: etoposide phosphate

Given IV

Drug: filgrastim

Given IV, subcutaneously

Drug: leucovorin calcium

Given IV or orally

Drug: mercaptopurine

Given orally

Drug: methotrexate

Given orally, intrathecally

Drug: pegaspargase

Given IM

Drug: prednisone

Given orally

Drug: therapeutic hydrocortisone

Given intrathecally

Drug: vincristine sulfate

Given IV

Procedure: 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.

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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 133 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Glen Lew, MD	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Investigator:	Rochelle A. Yanofsky, MD	CancerCare Manitoba

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000495359, COG-AALL0433
Study First Received:	September 26, 2006
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00381680
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

B-cell childhood acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia

Study placed in the following topic categories:

Dexamethasone
Prednisone
Leukemia, Lymphoid
Hydrocortisone
Leucovorin
Cyclophosphamide
6-Mercaptopurine
Etoposide phosphate
Lymphoma, B-Cell
Pegaspargase
Leukemia
Burkitt's lymphoma
Methotrexate
Epstein-Barr Virus Infections
Etoposide

Lymphoma
Cytarabine
Dexamethasone acetate
Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Cortisol succinate
Vincristine
Recurrence
Doxorubicin
Herpesviridae Infections
Folic Acid
Virus Diseases
Calcium, Dietary
Lymphatic Diseases

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Tumor Virus Infections
Antiemetics
Reproductive Control Agents
Antibiotics, Antineoplastic
Hormones
Neoplasms, Experimental

Vitamins
Therapeutic Uses
Abortifacient Agents
Micronutrients
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Vitamin B Complex
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Growth Substances
Mitosis Modulators
Gastrointestinal Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009