Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
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| ClinicalTrials.gov Identifier: NCT00103285 |
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Recruitment Status :
Completed
First Posted : February 8, 2005
Results First Posted : July 11, 2018
Last Update Posted : June 14, 2021
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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 randomized phase III trial is studying different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia. 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) may kill more cancer cells.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Lymphoblastic Leukemia Childhood B Acute Lymphoblastic Leukemia | Radiation: 3-Dimensional Conformal Radiation Therapy Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Drug: Leucovorin Calcium Drug: Mercaptopurine Drug: Methotrexate Drug: Pegaspargase Drug: Thioguanine Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 5377 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Standard Risk B-precursor Acute Lymphoblastic Leukemia (ALL) |
| Actual Study Start Date : | April 11, 2005 |
| Actual Primary Completion Date : | December 30, 2013 |
| Actual Study Completion Date : | March 31, 2021 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group 0 Induction Therapy
All patients receive cytarabine intrathecally (IT) on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) (may give IV over 1 to 2 hours) on day 4, 5, or 6; and methotrexate IT on days 8 and 29 (and days 15 and 22 for patients with CNS3 disease). Patients with Down syndrome (DS) receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT. Patients are assessed for response on day 29. Patients with M1 bone marrow AND minimal residual disease (MRD) < 0.1% OR MRD >= 0.1% and < 1% proceed to therapy in part II. Patients with M2 bone marrow OR M1 bone marrow AND MRD >= 1% proceed to extended induction therapy. Patients with M3 bone marrow are removed from the study.
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Drug: Cytarabine
Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Group 1-SR-low ALL, Arm I (combination chemotherapy)
Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard delayed intensification (DI) therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years
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Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV or IT
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Group 1-SR-low ALL, arm II (combination chemotherapy)
Patients receive experimental consolidation therapy, experimental interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Group 2-SR-avg ALL, arm I (combination chemotherapy)
Patients receive standard consolidation therapy, standard interim maintenance therapy, and standard DI therapy as in group 1, arm I, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV or IT
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Thioguanine Given PO
Other Names:
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Experimental: Group 2-SR-avg ALL, arm II (combination chemotherapy)
Patients receive standard consolidation therapy, augmented interim maintenance therapy, augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV or IT
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Group 2-SR-avg ALL, arm III (combination chemotherapy)
Patients receive intensified consolidation therapy, standard interim maintenance therapy, and standard DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV or IT
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Group 2-SR-avg ALL, arm IV (combination chemotherapy)
Patients receive intensified consolidation therapy, augmented interim maintenance therapy, and augmented DI therapy, followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV or IT
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Group 3-SR-high ALL, combination chemotherapy
Patients receive intensified consolidation therapy, augmented interim maintenance therapy (2 courses), and augmented DI therapy (2 courses), followed by maintenance therapy. Therapies are given by mouth, injection, and infusion for up to 2 or 3 years.
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Radiation: 3-Dimensional Conformal Radiation Therapy
Some patients undergo cranial radiotherapy
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV or SC
Other Names:
Drug: Dexamethasone Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride Given IV or IT
Other Names:
Drug: Leucovorin Calcium Given PO
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IM or IT
Other Names:
Drug: Pegaspargase Given IM
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Event-free Survival (EFS) for SR-Average ALL Patients [ Time Frame: 6 years ]EFS for SR-Average with standard and Intensified Consolidation. Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
- Event-free Survival (EFS) for SR-Low Patients [ Time Frame: 6 years ]Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Secondary Outcome Measures :
- Health-related Quality of Life Relative to Physical, Social and Emotional Impairment [ Time Frame: At 1, 6 and 12 months after diagnosis and, 3 months post-therapy ]To identify potentially modifiable factors associated with impaired health related quality of life (HRQOL) at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study.Standardized scores will be computed for child function using the gender and age-adjusted scores available from normative data from a healthy population of about 10,000 children. The various domains of family functioning will be assessed using well-validated instruments and analyzed as a dichotomous variable (impaired vs. non-impaired family functioning). Multiple regression analysis will be used to test the effect of family functioning (adjusted for therapy given, age at diagnosis, gender, socioeconomic status and other factors) on child function.
- Event-Free Survival Probability According to MRD Status End Induction (Day 29) [ Time Frame: MRD at Day 29 of therapy ]Event-Free survival by Day 29 MRD status (negative vs positive), Event Free Probability (time from study entry to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
- Overall Survival Probability (OS) According to Induction Day 29 MRD Status [ Time Frame: Overall Survival Probability of 6 years ]Overall survival by Day 29 MRD status (negative vs positive), Overall survival defined as time from study entry to death or date of last contact for patients who are alive.
- Early Marrow Status (EMS) by MRD Status End Induction (Day 29) [ Time Frame: Early Marrow Status at Day 15, MRD Status at Day 29 of therapy. ]Early Marrow Status defined as M1 versus M2/M3 marrow is correlated with MRD (Positive vs. Negative)
- Optimal Time Point for Advance Health Related Quality of Life Intervention [ Time Frame: At 1 month after diagnosis and 3 months post-therapy. ]Percentage of patients with elevated Anxiety.
- Event-free Survival (EFS) for SR-High Patients. [ Time Frame: 6 years ]Event Free Probability where EFS time is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
- Event-Free Survival (EFS) for Low MRD (Negative) Subjects by Genetic Subset (TEL/Trisomy Positive vs Negative) [ Time Frame: 6 years ]Event-free probability where EFS is defined as time from randomization to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 1 Year to 9 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients must be enrolled on AALL03B1 prior to enrollment on AALL0331
- Initial white blood cells (WBC) < 50,000/ul
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Newly diagnosed B-precursor acute lymphoblastic leukemia
- Standard-risk (SR) disease meeting 1 of the following criteria:
- SR-average by age and WBC
- No unfavorable features
- Rapid early responder (RER) by day 15
- CNS 1 or 2
- Minimal residual disease (MRD) negative on day 29
- Trisomies of 4, 10, and 17 or TEL-AML1 translocation and RER and CNS2 allowed
- SR-low by age and WBC
- No unfavorable features
- RER by day 15
- MRD negative on day 29
- CNS1
- Favorable cytogenetics-trisomies of 4, 10, and 17 or TEL-AML translocation
- SR-high
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Unfavorable features meeting ≥ 1 of the following criteria:
- MLL rearrangements and RER
- Steroid pretreatment
- CNS3
- Slow early responder by morphology or MRD
- Patients with Down syndrome are allowed
- Patients with overt testicular disease are not eligible for this study, but may be eligible for AALL0232
- Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the central nervous system [CNS] status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment
- Patients receiving prior steroid therapy may be eligible for AALL0331 study
- Patients with a contraindication to additional asparaginase therapy, following Induction, are not eligible for the Standard Risk-Low study, and should be removed from protocol therapy at the end of Induction
- Patients who are assigned to the standard risk-average group following Induction and who meet the HRQOL
- Age at diagnosis >= 2 years (note that this is a more restrictive age range than for the therapeutic component of the study)
- At least one parent with reading comprehension of English or Spanish languages for which validated surveys exist
- Diagnosis at one of the institutions participating in this limited institution correlative study
- A parent or legal guardian must sign a written informed consent/parental permission for all patients
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
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): NCT00103285
Locations
Show 236 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Kelly W Maloney | Children's Oncology Group |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00103285 |
| Other Study ID Numbers: |
AALL0331 NCI-2009-00302 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 05-340 COG-AALL0331 CDR0000409589 AALL0331 ( Other Identifier: Children's Oncology Group ) AALL0331 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
| First Posted: | February 8, 2005 Key Record Dates |
| Results First Posted: | July 11, 2018 |
| Last Update Posted: | June 14, 2021 |
| Last Verified: | April 2021 |
Additional relevant MeSH terms:
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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Calcium, Dietary Leucovorin Folic Acid Cytarabine Dexamethasone Dexamethasone acetate |
Cyclophosphamide Doxorubicin Liposomal doxorubicin Methotrexate Vincristine Asparaginase Mercaptopurine Pegaspargase Thioguanine BB 1101 Calcium 2-Aminopurine Levoleucovorin Immunosuppressive Agents Immunologic Factors |