Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma
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| ClinicalTrials.gov Identifier: NCT01190930 |
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Recruitment Status :
Active, not recruiting
First Posted : August 30, 2010
Last Update Posted : March 21, 2018
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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Brief Summary:
This partially randomized phase III trial studies different combinations of risk-adapted chemotherapy regimens and their side effects and comparing how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia or B-lineage lymphoblastic lymphoma that is found only in the tissue or organ where it began (localized). Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Adult B Lymphoblastic Lymphoma Childhood B Acute Lymphoblastic Leukemia Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 Childhood B Lymphoblastic Lymphoma Down Syndrome Stage I B Lymphoblastic Lymphoma Stage II B Lymphoblastic Lymphoma Untreated Adult Acute Lymphoblastic Leukemia Untreated Childhood Acute Lymphoblastic Leukemia | Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Leucovorin Calcium Drug: Mercaptopurine Drug: Methotrexate Drug: Pegaspargase Other: Quality-of-Life Assessment Other: Questionnaire Administration Drug: Thioguanine Drug: Vincristine Sulfate | Phase 3 |
Show Detailed Description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 9022 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Treatment of Patients With Newly Diagnosed Standard Risk B-Lymphoblastic Leukemia (B-ALL) or Localized B-Lineage Lymphoblastic Lymphoma (B-LLy) |
| Study Start Date : | August 2010 |
| Estimated Primary Completion Date : | March 2020 |
| Estimated Study Completion Date : | March 2020 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Down syndrome
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
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Drug: Dexamethasone
Given orally (PO) or IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, PO, or IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
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Drug: Dexamethasone
Given orally (PO) or IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, PO, or IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
|
Drug: Dexamethasone
Given orally (PO) or IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, PO, or IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
|
Drug: Dexamethasone
Given orally (PO) or IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, PO, or IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine Given IT, IV, or SC
Other Names:
Drug: Dexamethasone Given orally (PO) or IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, PO, or IV
Other Names:
Drug: Pegaspargase Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
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Drug: Dexamethasone
Given orally (PO) or IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT, PO, or IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Determination of whether less intensive therapy will maintain DFS >= 95% for LR patients randomized to 1 of 2 low-intensity regimens [ Time Frame: Time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]The 5-year DFS for these patients will be estimated on the 2 low intensity regimens. Interim analysis based on the estimated hazard rate will also be conducted, for each of the 2 low intensity regimens to protect against lower DFS for the LR patients.
- Determination of whether the 5-year DFS in AR patients is adversely affected by the reduced pulses in maintenance [ Time Frame: Every 4 weeks versus every 8 weeks from the start of reduced pulse maintenance, assessed up to 5 years ]If it is found that there is a decrease in DFS due to the reduced pulses, comparison of outcomes between the two MTX regimens will be restricted to the every 4 week pulses arms. A Cox proportional hazards model will be used to test for quantitative interaction in this 2x2 factorial design.
- DFS for B-LLy patients [ Time Frame: Time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]EFS rate will be estimated for this group of patients. The 95% confidence interval will be computed for the same. Biology data captured for these patients will be summarized.
- DFS for Down syndrome patients [ Time Frame: Time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]The 5-year DFS for these patients will be estimated on modified therapy.
- Improvement in DFS from 93% to 96% in AR patients based on the methotrexate randomization [ Time Frame: Time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years ]All power calculations are based on the assumption of proportional hazards, and using the log rank test (alpha = 5%) with 5 planned analyses of the data for interim monitoring purposes (MTX question for AR patients). The study will also be monitored for futility.
Secondary Outcome Measures :
- Burden of therapy in AR patients overall at different time points during and at the end of therapy [ Time Frame: Up to 30 months after beginning of maintenance (off-therapy time point for boys) ]Assessed by the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), the Child Vulnerability Scale, and by the Behavior Assessment Scales of Children-Second Edition, Parent Rating Scale (BASC-2 PRS). Standardized scores for the sub-scales of the PedsQL 4.0 will be calculated using age and gender specific normative data.
- Burden of therapy in AR patients randomized to every 4-week vs every 12-week pulses during maintenance therapy [ Time Frame: Up to 30 months after beginning of Maintenance (off-therapy time point for boys) ]Assessed by the Pediatric Quality of Life Instrument scores, the Child Vulnerability Scale, and emotional symptoms (measured by the BASC-2 PRS), adjusting for age, gender, and family income. Comparison of differences in means (of the continuous measures) between the 2 randomization groups with 2-sample t-tests will be done. If the continuous data are not normally distributed, a non-parametric statistical measure will be used.
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| Ages Eligible for Study: | 1 Year to 30 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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B-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0932
- Note: B-LLy patients are not eligible for AALL08B1, and can enroll directly onto AALL0932
- B-ALL patients must have an initial white blood cell count < 50,000/uL
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Patients must have newly diagnosed National Cancer Institute (NCI) Standard Risk B-ALL or B-LLy Murphy stages I or II; patients with Down syndrome are also eligible
- Note: for B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
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With the exception of steroid pretreatment (defined below) or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL0932
- Patients receiving prior steroid therapy may be eligible for AALL0932
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Patients with central nervous system 3 (CNS3) leukemia
- CNS status must be known prior to enrollment; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); B-LLy patients with CNS3 disease are not eligible for this protocol or the COG HR ALL protocol; it is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; this is allowed prior to registration; systemic chemotherapy must begin within 72 hours of the first dose of intrathecal therapy
- B-ALL patients with testicular leukemia are not eligible for AALL0932
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For B-LLy patients the following additional exclusion criteria apply:
- T-lymphoblastic lymphoma
- Morphologically unclassifiable lymphoma
- Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma
- CNS3-positive disease or testicular involvement
- M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow
- Female patients who are pregnant are ineligible
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01190930
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Anne Angiolillo | Children's Oncology Group |
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT01190930 History of Changes |
| Other Study ID Numbers: |
AALL0932 NCI-2011-02599 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000683227 AALL0932 ( Other Identifier: Children's Oncology Group ) AALL0932 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | August 30, 2010 Key Record Dates |
| Last Update Posted: | March 21, 2018 |
| Last Verified: | March 2018 |
Additional relevant MeSH terms:
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Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Non-Hodgkin Down Syndrome Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Intellectual Disability Neurobehavioral Manifestations Neurologic Manifestations |
Nervous System Diseases Abnormalities, Multiple Congenital Abnormalities Chromosome Disorders Genetic Diseases, Inborn Dexamethasone acetate Dexamethasone Liposomal doxorubicin Pegaspargase Cyclophosphamide Doxorubicin Methotrexate Cytarabine Vincristine Asparaginase |