Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00408005
First received: December 4, 2006
Last updated: September 16, 2014
Last verified: July 2014
  Purpose

This randomized phase III trial is studying different combination chemotherapy regimens and their side effects and comparing how well they work in treating young patients with newly diagnosed T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma. 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. It is not yet known which combination chemotherapy regimen is more effective in treating T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma.


Condition Intervention Phase
Contiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Stage II Adult T-cell Leukemia/Lymphoma
Stage II Childhood Lymphoblastic Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Childhood Lymphoblastic Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Childhood Lymphoblastic Lymphoma
T-cell Adult Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: cytarabine
Drug: vincristine sulfate
Drug: daunorubicin hydrochloride
Drug: prednisone
Drug: pegaspargase
Drug: methotrexate
Drug: leucovorin calcium
Drug: cyclophosphamide
Drug: mercaptopurine
Radiation: radiation therapy
Drug: nelarabine
Drug: doxorubicin hydrochloride
Drug: asparaginase
Drug: dexamethasone
Drug: thioguanine
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensified Methotrexate, Nelarabine (Compound 506U78) and Augmented BFM Therapy for Children and Young Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) or T-Cell Lymphoblastic Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free survival (EFS) after initial remission [ Time Frame: At 4 years ] [ Designated as safety issue: No ]
    This outcome can be modeled reasonably well by a linear decreasing hazard rate with no appreciable risk of failure after completion of year 4. EFS events include any type of relapse, death in remission or second malignant neoplasm. "Intent-to-treat" analyses (i.e. based on the regimen to which patients are initially randomized) will be the primary approach used to assess treatment efficacy.

  • Nelarabine toxicity assessment by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to week 43 ] [ Designated as safety issue: Yes ]
    Compared directly to their randomized control not receiving nelarabine with additional examination of the comparison within the separate methotrexate regimen subsets. These comparisons will focus on grade 3 or higher non-hematologic toxicities. The overall incidence of selected neurologic toxicities will also be monitored since these represent an important target category for nelarabine toxicity.

  • Incidence of toxicities of combination chemotherapy with vs without nelarabine as assessed by NCI CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Efficacy of combination chemotherapy with vs without nelarabine [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    "Intent-to-treat" analyses (i.e. based on the regimen to which patients are initially randomized) will be the primary approach used to assess treatment efficacy.

  • Incidence of toxicities of high-dose methotrexate (with leucovorin calcium rescue) and mercaptopurine vs escalating-dose methotrexate (without leucovorin calcium rescue) and pegaspargase [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Efficacy of high-dose methotrexate (with leucovorin calcium rescue) and mercaptopurine vs escalating-dose methotrexate (without leucovorin calcium rescue) and pegaspargase [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Analyses will be performed regularly to assess the possibility of an interaction effect (using a Cox regression likelihood ratio test) which will assess the four individual treatment regimens in the 2 x 2 design to see if a non-proportional hazards effect occurs for the combinations of the two main effect factors. Since the comparison of the methotrexate regimens utilizes a selection type analysis, no futility testing will be used for that comparison.


Secondary Outcome Measures:
  • Incidence of CNS relapse [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Examined for various treatment regimen comparisons, and in the subset of patients who will not receive XRT CNS prophylaxis.

  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 1900
Study Start Date: January 2007
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (Consolidation chemotherapy)
Patients receive methotrexate IT on days 1, 8, 15, and 22; cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine IV over 15-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43 and 50; and pegaspargase IM or IV over 1-2 hours on days 15 and 43. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 11-12, 15-19, and 22-26. (DS patients excluded as of 09/29/10.) Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT (1,200 cGy/dose) QD on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Deltra
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Radiation: radiation therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (Consolidation chemotherapy)
Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; methotrexate IT on days 15, 22, 57, and 64; cyclophosphamide IV over 30 minutes on days 8 and 50; cytarabine IV over 15-30 minutes or SC on days 8-11, 15-18, 50-53 and 57-60; mercaptopurine PO on days 8-21 and 50-63; vincristine sulfate IV on days 22, 29, 64, and 71; and pegaspargase IM or IV over 1-2 hours on days 22 and 64. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy on days 15, 22-26, and 29-33 (DS patients excluded as of 09/29/10). (Patients with intermediate-risk or high-risk disease (CNS1 or CNS2) undergo prophylactic CRT QD on days 22-28 and 29-35.
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Deltra
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Radiation: radiation therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: nelarabine
Given IV
Other Names:
  • 506U78
  • Arranon
  • GW506U78
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm III (Consolidation chemotherapy)
Patients receive methotrexate, cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and pegaspargase as in arm I. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm I (DS patients excluded as of 09/29/10).
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Deltra
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm IV (Consolidation chemotherapy)
Patients receive nelarabine, methotrexate, cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and pegaspargase as in arm II. Patients with persistent testicular disease or with DS and testicular disease undergo testicular radiotherapy as in arm II (DS patients excluded as of 09/29/10).
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Deltra
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: nelarabine
Given IV
Other Names:
  • 506U78
  • Arranon
  • GW506U78
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm I (Interim maintenance chemotherapy)

Patients receive vincristine sulfate IV and escalating doses of methotrexate IV on days 1, 11, 21, 31, and 41; pegaspargase* IM or IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Patients with DS also receive leucovorin calcium PO 48 and 60 hours after each methotrexate IT dose (DS patients excluded as of 09/29/10).

Note: *Patients with an allergy to pegaspargase receive Erwinia asparaginase on days 2, 4, 6, 8, 10, 12, 22, 24, 26, 28, 30, and 32.

Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: asparaginase
Given IM or IV
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (Interim maintenance chemotherapy)
Patients receive vincristine sulfate, escalating doses of methotrexate, pegaspargase, and methotrexate IT as in arm I.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm III (Interim maintenance chemotherapy)
Patients receive HDMTX IV over 24 hours and vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO on days 1-56; and methotrexate IT on days 1 and 29. Beginning 42 hours after the start of HDMTX, patients also receive leucovorin calcium IV or PO once every 6 hours for 3 doses.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm IV (Interim maintenance chemotherapy)
Patients receive HDMTX, vincristine sulfate, mercaptopurine, methotrexate IT, and leucovorin calcium as in arm III.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm I (Delayed intensification chemotherapy)
Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age and for patients with DS); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients with DS also receive leucovorin calcium PO at 48 and 60 hours after each methotrexate dose (DS patients excluded as of 09/29/10).
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: leucovorin calcium
Given PO
Other Names:
  • CF
  • CFR
  • LV
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (Delayed intensification chemotherapy)
Patients receive vincristine sulfate IV on days 1, 8, 15, and 50; dexamethasone IV or PO BID on days 1-21 (for patients < 10 years of age) OR on days 1-7 and 15-21 (for patients >= 10 years of age); doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6 AND day 50; methotrexate IT on days 1, 36, and 43; nelarabine IV over 60 minutes on days 29-33; cyclophosphamide IV over 30 minutes on day 36; cytarabine IV over 15-30 minutes or SC on days 36-39 and 43-46; and thioguanine PO on days 36-49.
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: nelarabine
Given IV
Other Names:
  • 506U78
  • Arranon
  • GW506U78
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: thioguanine
Given PO
Other Name: 6-TG
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm III (Delayed intensification chemotherapy)
Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, methotrexate IT, cyclophosphamide, cytarabine, and thioguanine as in arm I. Patients with intermediate- or high-risk disease (CNS1 or CNS2 disease) undergo prophylactic CRT (1,200 cGy/dose) QD on days 50-54 and 57-59.
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: thioguanine
Given PO
Other Name: 6-TG
Active Comparator: Arm IV (Delayed intensification chemotherapy)
Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, methotrexate IT, nelarabine, cyclophosphamide, cytarabine, and thioguanine as in arm II. Patients with intermediate- or high-risk disease (CNS 1 or CNS2 disease) undergo prophylactic CRT on days 50-54 and 57-59.
Drug: cytarabine
Given IT, IV, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: pegaspargase
Given IM or IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: nelarabine
Given IV
Other Names:
  • 506U78
  • Arranon
  • GW506U78
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: thioguanine
Given PO
Other Name: 6-TG
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm I (Maintenance chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (Maintenance chemotherapy)
Patients receive vincristine sulfate IV on days 1 and 57; dexamethasone PO on days 1-5 and 57-61; mercaptopurine PO QD on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; methotrexate IT on day 1; and nelarabine IV over 60 minutes on days 29-33. Treatment (that includes nelarabine) repeats every 84 days for 3 courses. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate IV on days 1 and 57; dexamethasone PO on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: nelarabine
Given IV
Other Names:
  • 506U78
  • Arranon
  • GW506U78
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm III (Maintenance chemotherapy)
Patients receive vincristine sulfate, dexamethasone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm I. Treatment repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 119) (for girls with T-ALL) and 3 years from the start of interim maintenance therapy (approximately week 171) (for boys with T-ALL).
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Radiation: radiation therapy
Some patients undergo testicular and/or prophylactic cranial RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm IV (Maintenance chemotherapy)
Patients receive vincristine sulfate, dexamethasone, mercaptopurine, methotrexate PO, methotrexate IT, and nelarabine as in arm II. Patients then receive treatment (without nelarabine) as follows: vincristine sulfate, dexamethasone, mercaptopurine, methotrexate PO, and methotrexate IT as in arm II. Treatment (without nelarabine) repeats every 84 days until the total duration of study treatment is 2 years from the start of interim maintenance therapy (approximately week 121) (for girls with T-ALL) and 3 years from the start of interim maintenance therapy (approximately week 173) (for boys with T-ALL).
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: methotrexate
Given IT or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: mercaptopurine
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: nelarabine
Given IV
Other Names:
  • 506U78
  • Arranon
  • GW506U78
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • T-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0434
  • Patients must have newly diagnosed T-ALL or T-lineage lymphoblastic lymphoma (T-NHL) stage II-IV; B-lineage lymphoblastic lymphoma will not be eligible for this study; a diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation [CD]19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a; if surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including transmission disequilibrium test (TdT), CD34 or CD99 will be assessed for expression; cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory
  • T-NHL PATIENTS:

    • For T-NHL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-NHL defined by the submitting institution will be accepted
  • Prior therapy restrictions

    • Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and/or IT cytarabine
    • IT 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 CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); systemic chemotherapy must begin within 72 hours of this IT therapy
    • Patients diagnosed as having T-NHL or T-ALL with respiratory distress or hyperleukocytosis may require steroids prior to the initiation of additional systemic therapy; they are eligible for AALL0434 and will be stratified, based on the initial complete blood count (CBC); steroid pretreatment may alter the risk group assessment; if the T-ALL patient's clinical status precludes a lumbar puncture within 48 hours of the initiation of steroid therapy, T-ALL patients CANNOT be classified as low risk and will be Intermediate or high risk based on the results of the day 29 marrow as above; patients with T-NHL who receive steroid pre-treatment will be classified as high risk; the dose and duration of previous steroid therapy should be carefully documented
    • For the management of airway compromise, patients who have received emergent chest irradiation up to 600 cGy will be eligible for this study
  • Patients with a prior seizure disorder requiring anti-convulsant therapy are not eligible to receive nelarabine; in addition, patients with pre-existing grade 2 (or greater) peripheral neurotoxicity, as determined prior to Induction treatment by the treating physician or a neurologist, are not eligible to receive nelarabine; these restrictions in eligibility are designed to prevent excessive nelarabine-induced central and peripheral neurotoxicity in at-risk patients; for the purposes of this study, this includes any patient that has received anticonvulsant therapy to prevent/treat seizures in the prior two years

Exclusion Criteria:

  • Pregnant or lactating females are ineligible
  • Patients with Down syndrome are ineligible to enroll onto this study
  • For T-NHL patients the following additional exclusion criteria apply:

    • B-precursor lymphoblastic lymphoma
    • Morphologically unclassifiable lymphoma
    • Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma
    • CNS3-positive or testicular involvement
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00408005

  Show 206 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Stuart Winter Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00408005     History of Changes
Other Study ID Numbers: NCI-2009-00307, NCI-2009-00307, CDR0000514500, COG-AALL0434, AALL0434, AALL0434, U10CA098543
Study First Received: December 4, 2006
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Methotrexate
Cytarabine
6-Mercaptopurine
Liposomal doxorubicin
Pegaspargase
Dexamethasone
Doxorubicin
Vincristine
Daunorubicin
Asparaginase
Thioguanine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Levoleucovorin

ClinicalTrials.gov processed this record on September 18, 2014