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Trial record 1 of 1 for:    NCT00408005
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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: November 20, 2014
Last verified: July 2014

December 4, 2006
November 20, 2014
January 2007
September 2017   (final data collection date for primary outcome measure)
  • 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.
  • Event-free survival after initial remission
  • Safety and efficacy of combination chemotherapy with vs without nelarabine
  • Safety and efficacy of high-dose methotrexate with leucovorin calcium rescue and mercaptopurine vs escalating-dose methotrexate without leucovorin calcium rescue and pegaspargase
  • Toxicity of nelarabine
Complete list of historical versions of study NCT00408005 on ClinicalTrials.gov Archive Site
  • 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 ]
  • CNS relapse
  • Overall survival
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma
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

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.

PRIMARY OBJECTIVES:

I. To determine, through randomization, the relative safety and efficacy of the addition of nelarabine (Compound 506U78) to augmented Berlin-Frankfurt-Münster (BFM) therapy (Regimen C, Children's Cancer Group [CCG]-1961).

II. To determine the relative safety and efficacy of high dose methotrexate (5 g/m^2) with leucovorin (leucovorin calcium) rescue compared to escalating methotrexate without leucovorin rescue plus pegaspargase (Capizzi I) delivered during interim maintenance.

III. To gain preliminary data on the use of nelarabine in patients with high risk T-cell lymphoblastic lymphoma and its effect on long-term survival.

SECONDARY OBJECTIVES:

I. To determine the relative safety and efficacy of withholding radiation in patients with low risk T-cell acute lymphoblastic leukemia (T-ALL), while treating Intermediate and high risk patients with 1200 cGy of prophylactic cranial radiation.

OUTLINE:

INDUCTION THERAPY: (weeks 1-5) Patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV and daunorubicin hydrochloride IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; pegaspargase intramuscularly (IM) or IV over 1-2 hours on day 4, 5, OR 6; and methotrexate (MTX) IT on days 8 and 29*. Patients with Down syndrome (DS) also receive leucovorin calcium PO at 48 and 60 hours after each MTX dose (DS patients excluded as of 09/29/10).

After completion of induction therapy, patients undergo risk assessment. Patients with M1 marrow and minimal residual disease (MRD) < 1% (defined as low- and intermediate-risk) proceed to consolidation therapy at day 36 or when blood counts recover (whichever occurs later). Patients with M2 marrow (5-25% blasts) and/or MRD >= 1% (defined as high-risk) proceed to consolidation therapy as soon as possible (i.e., they should not wait until day 36 or for blood counts to recover). Patients with M3 marrow (>= 25% blasts) (defined as induction failure) proceed to consolidation therapy as soon as possible.

NOTE: *Patients with CNS3 disease also receive MTX IT on days 15 and 22.

CONSOLIDATION THERAPY: (weeks 6-13) During the safety phase portion of the study, patients with low-risk or intermediate-risk disease are randomized to arms I or III. Patients with high-risk disease are randomized to arms I, II, III, or IV. (safety phase closed for accrual as of 09/29/10) During the efficacy phase portion of the study, patients with low-risk* disease are randomized to arms I and III. Patients with intermediate-risk or high-risk** disease are randomized to arms I, II, III, or IV. The safety phase ends when the first 20 high-risk patients to receive nelarabine have been evaluated. Patients with DS are nonrandomly assigned to arm I (DS patients excluded as of 09/29/10). Patients with induction failure*** are nonrandomly assigned to arm IV.

NOTE: *Patients with T-cell lymphoblastic lymphoma (T-NHL) are nonrandomly assigned to arm I.

NOTE: ** Patients with T-NHL are randomly assigned to arms I or II without cranial radiotherapy.

NOTE: *** Patients with T-NHL are nonrandomly assigned to arm II.

ARM I: Patients receive MTX 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 subcutaneously (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 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 cranial radiotherapy (CRT) (1,200 cGy/dose) once daily on days 15-21 and 22-28. Patients with low-risk disease do not undergo CRT.

NOTE: *Patients with CNS3 disease omit MTX IT on days 15 and 22; patients with high-risk disease omit MTX IT on day 1 and add an extra dose at day 29.

ARM II: Patients receive nelarabine IV over 60 minutes on days 1-5 and 43-47; MTX 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; oral mercaptopurine 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 once daily on days 22-28 and 29-35.

NOTE: *Patients with CNS3 disease omit MTX IT on day 22.

ARM III: Patients receive MTX, 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).

ARM IV: 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). Once blood counts recover, patients proceed to interim maintenance therapy according to their randomized/assigned arm. Patients not achieving M1 marrow by the end of consolidation therapy are removed from the study.

INTERIM MAINTENANCE THERAPY (weeks 14-21 for arms I and III; weeks 17-24 for arms II and IV):

ARM I: 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 T-NHL are randomized or assigned to arms I or II only.

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.

ARM II: Patients* receive vincristine sulfate, escalating doses of methotrexate, pegaspargase, and methotrexate IT as in arm I.

ARM III: Patients receive high-dose methotrexate (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 orally once every 6 hours for 3 doses.

ARM IV: Patients receive HDMTX, vincristine sulfate, mercaptopurine, methotrexate IT, and leucovorin calcium as in arm III.

Once blood counts recover, patients proceed to delayed intensification therapy according to their randomized/assigned arm.

DELAYED INTENSIFICATION THERAPY (weeks 22-30 for arms I and III; weeks 25-33 for arms II and IV):

ARM I: 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 over 1-15 minutes on days 1, 8, and 15; pegaspargase IM or IV over 1-2 hours on day 4, 5, OR 6, AND day 43; MTX 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).

NOTE: *T-NHL patients with standard-risk are nonrandomly assigned to arm I.

ARM II: 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 over 1-15 minutes 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 on days 36-39 and 43-46; and thioguanine PO on days 36-49.

NOTE: ** T-NHL patients with induction failure are nonrandomly assigned to arm II.

ARM III: 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.

ARM IV: 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.

All patients with CNS3 disease at diagnosis undergo CRT (1,800cGy/dose) QD on days 50-54 and 57-61. Once blood counts recover, patients proceed to maintenance therapy according to their randomized/assigned arm.

MAINTENANCE THERAPY (week 31 until the end of therapy for arms I and III; weeks 34-69 for arms II and IV):

ARM I: 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).

NOTE: * Patients with T-NHL and standard-risk are nonrandomly assigned to arm I.

NOTE: **Patients with low-risk disease receive methotrexate IT, instead of methotrexate PO, on day 29 during the first 4 courses of therapy.

ARM II: 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; MTX 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).

NOTE: *** T-NHL patients with induction failure are nonrandomly assigned to arm II.

ARM III: 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).

NOTE: *Patients with low-risk disease receive methotrexate IT, instead of methotrexate PO, on day 29 during the first 4 courses of therapy.

ARM IV: 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).

After completion of study therapy, patients are followed periodically for at least 10 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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
  • Drug: asparaginase
    Given IM or IV
    Other Names:
    • ASNase
    • Colaspase
    • Crasnitin
    • Elspar
    • L-ASP
  • 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 (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.
    Interventions:
    • 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: doxorubicin hydrochloride
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • 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
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: daunorubicin hydrochloride
    • Drug: prednisone
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: cyclophosphamide
    • Drug: mercaptopurine
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: vincristine sulfate
    • Drug: daunorubicin hydrochloride
    • Drug: prednisone
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: cyclophosphamide
    • Drug: mercaptopurine
    • Drug: nelarabine
    • Other: laboratory biomarker analysis
  • 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.

    Interventions:
    • Drug: vincristine sulfate
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: leucovorin calcium
    • Drug: asparaginase
    • Other: laboratory biomarker analysis
  • Active Comparator: Arm II (Interim maintenance chemotherapy)
    Patients receive vincristine sulfate, escalating doses of methotrexate, pegaspargase, and methotrexate IT as in arm I.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: leucovorin calcium
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: methotrexate
    • Drug: leucovorin calcium
    • Drug: mercaptopurine
    • Other: laboratory biomarker analysis
  • Active Comparator: Arm IV (Interim maintenance chemotherapy)
    Patients receive HDMTX, vincristine sulfate, mercaptopurine, methotrexate IT, and leucovorin calcium as in arm III.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: methotrexate
    • Drug: leucovorin calcium
    • Drug: mercaptopurine
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: leucovorin calcium
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: dexamethasone
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: pegaspargase
    • Drug: cyclophosphamide
    • Drug: nelarabine
    • Drug: doxorubicin hydrochloride
    • Drug: dexamethasone
    • Drug: thioguanine
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: pegaspargase
    • Drug: cyclophosphamide
    • Drug: doxorubicin hydrochloride
    • Drug: dexamethasone
    • Drug: thioguanine
  • 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.
    Interventions:
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: cyclophosphamide
    • Drug: nelarabine
    • Drug: doxorubicin hydrochloride
    • Drug: dexamethasone
    • Drug: thioguanine
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: vincristine sulfate
    • Drug: methotrexate
    • Drug: mercaptopurine
    • Drug: dexamethasone
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: vincristine sulfate
    • Drug: methotrexate
    • Drug: mercaptopurine
    • Drug: nelarabine
    • Drug: dexamethasone
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: methotrexate
    • Drug: mercaptopurine
    • Radiation: radiation therapy
    • Drug: dexamethasone
    • Other: laboratory biomarker analysis
  • 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).
    Interventions:
    • Drug: vincristine sulfate
    • Drug: methotrexate
    • Drug: mercaptopurine
    • Drug: nelarabine
    • Drug: dexamethasone
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1900
Not Provided
September 2017   (final data collection date for primary outcome measure)

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
Both
1 Year to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   New Zealand,   Switzerland
 
NCT00408005
NCI-2009-00307, NCI-2009-00307, CDR0000514500, COG-AALL0434, AALL0434, AALL0434, U10CA098543
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Stuart Winter Children's Oncology Group
National Cancer Institute (NCI)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP