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Trial record 1 of 1 for:    NCT00873093
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Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00873093
First received: March 31, 2009
Last updated: November 30, 2016
Last verified: November 2016
  Purpose
This pilot, phase II trial studies the side effects of giving bortezomib together with combination chemotherapy and to see how well it works in treating young patients with relapsed acute lymphoblastic leukemia or lymphoblastic lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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 bortezomib together with combination chemotherapy may kill more cancer cells.

Condition Intervention Phase
B-cell Adult Acute Lymphoblastic Leukemia B-cell Childhood Acute Lymphoblastic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Lymphoblastic Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Lymphoblastic Lymphoma T-cell Adult Acute Lymphoblastic Leukemia T-cell Childhood Acute Lymphoblastic Leukemia Drug: L-asparaginase Drug: doxorubicin hydrochloride Drug: therapeutic hydrocortisone Drug: vincristine sulfate Drug: cytarabine Drug: prednisone Drug: bortezomib Drug: pegaspargase Drug: methotrexate Drug: etoposide phosphate Drug: cyclophosphamide Biological: filgrastim Drug: leucovorin calcium Other: laboratory biomarker analysis Drug: High Dose MTX Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Pilot Trial of Bortezomib (PS-341, Velcade) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy [ Time Frame: The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy. ]
    The percentage of eligible and evaluable patients who have achieved complete response at the end Block 1 of re-induction therapy.

  • Event Free Survival [ Time Frame: 4 months after enrollment ]
    Percentage of patients who were event free at 4 months

  • Toxic Death Rate [ Time Frame: 4 months ]
    The proportion of toxic death rate among all eligible patients.

  • Severe Adverse Events (SAE) Rate. [ Time Frame: 4 months ]
    The proportion of SAE rate among all eligible patients


Secondary Outcome Measures:
  • Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1 [ Time Frame: End of Block 1 (Day 36 of Block 1) of re-induction therapy ]
    Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 1.

  • Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 2 [ Time Frame: End of Block 2 (Day 36 of Block 2) of re-induction therapy ]
    Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 2.

  • Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3 [ Time Frame: End of Block 3 (Day 36 of Block 3) of re-induction therapy ]
    Percentage of eligible and evaluable patients with MRD < 0.01% among those who had successful MRD determination at the end of Block 3.


Other Outcome Measures:
  • NF-kB Activity [ Time Frame: Up to 5 years ]
    NF-kB activity will be measured as a continuous variable (ng NF-kB/ug protein). Differences in NF-kB activity between time points will be assessed using summary statistics such as mean, standard deviation, and range.

  • Expression of Apoptotic and Cell Cycle Proteins Assessed by Using Gene and Tissue Microarrays and Immunoblots [ Time Frame: Up to 5 years ]
    Characterized using descriptive statistics. If differences are noted between pre- and post-treatment protein expression, pairwise comparisons will be made using paired t-test or an equivalent nonparametric test. The normality assumption will be assessed on the log-transformed data prior to paired t-test evaluation.

  • Change in Stem Cell Percentage [ Time Frame: Baseline to post-treatment with bortezomib ]
    Will use descriptive statistics to assess mean +/- standard deviation for stem cell percentage before and after bortezomib treatment. If there appears to be a difference in responders vs. non-responders, stem cell percentage differences between responders and non-responders will be compared using a paired t-test or equivalent nonparametric test.

  • Plasma Concentration-time Profiles [ Time Frame: Up to day 8 of block 2 ]
    Will be analyzed using descriptive statistics and will be graphically displayed by age group and stratum. PK data will be analyzed using methods such as nonlinear mixed effects modeling to estimate bortezomib clearance and volume of distribution (and the associated 95% confidence intervals) in each age group (2-11 years and 12-16 years of age).

  • Pharmacokinetics (PK) of Bortezomib in Patients Receiving Multi-agent Combination Therapy. [ Time Frame: Day 8 of blocks 1 and 2 ]
    This outcome measure cannot be reported due to the data used for analysis was not collected.


Enrollment: 148
Study Start Date: March 2009
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
Drug: L-asparaginase
Given IM 6000 IU/m2/dose Days 2 and 9
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV 60 mg/m2/dose on Day 1
Other Names:
  • ADM
  • ADR
  • Adria
Drug: therapeutic hydrocortisone
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Drug: cytarabine
Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given PO or IV 40 mg/m2/day on Days 1-28
Other Names:
  • DeCortin
  • Deltra
Drug: bortezomib
Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: pegaspargase
Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide phosphate
Given IV 100 mg/m2/dose on Days 1-5
Other Names:
  • ETOP
  • Etopophos
Drug: cyclophosphamide
Given IV 440 mg/m2/dose on Days 1-5
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC 5 micrograms/kg/dose Only on Day 6
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given PO or IV 15mg/m2/dose q6h x 3 doses
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies
Drug: High Dose MTX
IV 5000 mg/m2/dose Block 2: Day 22
Other Names:
  • methotrexate
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
Experimental: Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
Drug: L-asparaginase
Given IM 6000 IU/m2/dose Days 2 and 9
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV 60 mg/m2/dose on Day 1
Other Names:
  • ADM
  • ADR
  • Adria
Drug: therapeutic hydrocortisone
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Drug: cytarabine
Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given PO or IV 40 mg/m2/day on Days 1-28
Other Names:
  • DeCortin
  • Deltra
Drug: bortezomib
Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: pegaspargase
Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide phosphate
Given IV 100 mg/m2/dose on Days 1-5
Other Names:
  • ETOP
  • Etopophos
Drug: cyclophosphamide
Given IV 440 mg/m2/dose on Days 1-5
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC 5 micrograms/kg/dose Only on Day 6
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given PO or IV 15mg/m2/dose q6h x 3 doses
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies
Drug: High Dose MTX
IV 5000 mg/m2/dose Block 2: Day 22
Other Names:
  • methotrexate
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
Experimental: Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
Drug: L-asparaginase
Given IM 6000 IU/m2/dose Days 2 and 9
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV 60 mg/m2/dose on Day 1
Other Names:
  • ADM
  • ADR
  • Adria
Drug: therapeutic hydrocortisone
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Drug: cytarabine
Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given PO or IV 40 mg/m2/day on Days 1-28
Other Names:
  • DeCortin
  • Deltra
Drug: bortezomib
Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: pegaspargase
Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide phosphate
Given IV 100 mg/m2/dose on Days 1-5
Other Names:
  • ETOP
  • Etopophos
Drug: cyclophosphamide
Given IV 440 mg/m2/dose on Days 1-5
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC 5 micrograms/kg/dose Only on Day 6
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given PO or IV 15mg/m2/dose q6h x 3 doses
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies
Drug: High Dose MTX
IV 5000 mg/m2/dose Block 2: Day 22
Other Names:
  • methotrexate
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
Experimental: T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
Drug: L-asparaginase
Given IM 6000 IU/m2/dose Days 2 and 9
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV 60 mg/m2/dose on Day 1
Other Names:
  • ADM
  • ADR
  • Adria
Drug: therapeutic hydrocortisone
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Drug: cytarabine
Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given PO or IV 40 mg/m2/day on Days 1-28
Other Names:
  • DeCortin
  • Deltra
Drug: bortezomib
Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: pegaspargase
Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide phosphate
Given IV 100 mg/m2/dose on Days 1-5
Other Names:
  • ETOP
  • Etopophos
Drug: cyclophosphamide
Given IV 440 mg/m2/dose on Days 1-5
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC 5 micrograms/kg/dose Only on Day 6
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given PO or IV 15mg/m2/dose q6h x 3 doses
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies
Drug: High Dose MTX
IV 5000 mg/m2/dose Block 2: Day 22
Other Names:
  • methotrexate
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
Experimental: T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
Drug: L-asparaginase
Given IM 6000 IU/m2/dose Days 2 and 9
Other Names:
  • ASNase
  • Colaspase
  • Crasnitin
  • Elspar
  • L-ASP
Drug: doxorubicin hydrochloride
Given IV 60 mg/m2/dose on Day 1
Other Names:
  • ADM
  • ADR
  • Adria
Drug: therapeutic hydrocortisone
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22
Other Names:
  • Aeroseb-HC
  • Barseb HC
  • Cetacort
  • Cort-Dome
  • Cortef
Drug: vincristine sulfate
Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22
Other Names:
  • liposomal vincristine
  • Marqibo
  • vincristine liposomal
  • vincristine sulfate liposome injection
Drug: cytarabine
Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given PO or IV 40 mg/m2/day on Days 1-28
Other Names:
  • DeCortin
  • Deltra
Drug: bortezomib
Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Drug: pegaspargase
Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: methotrexate
Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: etoposide phosphate
Given IV 100 mg/m2/dose on Days 1-5
Other Names:
  • ETOP
  • Etopophos
Drug: cyclophosphamide
Given IV 440 mg/m2/dose on Days 1-5
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: filgrastim
Given IV or SC 5 micrograms/kg/dose Only on Day 6
Other Names:
  • G-CSF
  • Neupogen
Drug: leucovorin calcium
Given PO or IV 15mg/m2/dose q6h x 3 doses
Other Names:
  • CF
  • CFR
  • LV
Other: laboratory biomarker analysis
Correlative studies
Drug: High Dose MTX
IV 5000 mg/m2/dose Block 2: Day 22
Other Names:
  • methotrexate
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 31 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis

    • Pre-B ALL in first early (< 36 months from diagnosis) isolated bone marrow (BM) or combined BM/extramedullary relapse; or
    • T-cell ALL in first isolated BM or combined relapse; or
    • T-LL in first relapse
  • Patients with leukemia must have had histologic verification of the malignancy at relapse, including immunophenotyping to confirm diagnosis
  • Patients with lymphoblastic lymphoma must have measurable disease documented by clinical, radiographic, or histologic criteria; patients must have relapsed or become refractory to conventional therapy
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study
  • Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
  • At least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy
  • At least 7 days since the completion of therapy with a biologic agent or donor lymphocyte infusions (DLI); for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • No evidence of active graft-vs-host disease (GVHD) and >= 4 months must have elapsed; must not be receiving GVHD prophylaxis
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 month to < 6 months (0.4 male, 0.4 female)
    • 6 months to < 1 year (0.5 male, 0.5 female)
    • 1 to < 2 years (0.6 male, 0.6 female)
    • 2 to < 6 years (0.8 male, 0.8 female)
    • 6 to < 10 years (1 male, 1 female)
    • 10 to < 13 years (1.2 male, 1.2 female)
    • 13 to < 16 years (1.5 male, 1.4 female)
    • >= 16 years (1.7 male, 1.4 female)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN for age, unless elevation due to leukemia infiltration
  • Shortening fraction of >= 27% by echocardiogram, or
  • Ejection fraction of >= 50% by gated radionuclide study
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >= 94% at sea level (> 90% if at high altitude)
  • No evidence of acute pulmonary infiltrates on chest radiograph
  • Patients with seizure disorder may be enrolled if on allowed anticonvulsants and well controlled; benzodiazepines and gabapentin are acceptable
  • Central nervous system (CNS) toxicity =< grade 2
  • Peripheral nervous system (PNS) toxicity < grade 3
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, FDA, and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Patients with Philadelphia chromosome positive ALL are not eligible unless refractory to at least one tyrosine kinase inhibitor (TKI) therapy; patients that are unable to tolerate TKI therapy due to toxicity are eligible
  • Patients with mature B-cell ALL, ie, leukemia with B-cell (soluble immunoglobulin [sIg] positive and kappa or lambda restricted positivity) ALL, with French-American-British (FAB) L3 morphology and/or a myc translocation, are not eligible
  • Extramedullary disease status: patients with isolated CNS disease or isolated testicular disease are not eligible
  • Patients with known optic nerve and/or retinal involvement are not eligible; patients presenting with visual disturbances should have an ophthalmological exam and, if indicated, an magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
  • Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible
  • Cumulative prior anthracycline exposure must not exceed 400 mg/m^2
  • Patients taking anticonvulsants known to activate the cytochrome p450 system, in particular anticonvulsants such as phenytoin, carbamazepine, and phenobarbital, are not eligible; benzodiazepines and gabapentin are acceptable
  • Patients who have previously received bortezomib or other proteasome inhibitors are not eligible
  • Patients who have a known allergy to doxorubicin, cytarabine, both etoposide and etopophos, boron, mannitol or bortezomib are not eligible
  • Patients who cannot receive any asparaginase products (E. Coli, PEG-asparaginase, or Erwinia asparaginase) on this study (eg, due to prior severe pancreatitis, stroke or other toxicity) are not eligible; patients who initially receive asparaginase, but must discontinue due to toxicity, remain eligible; patients with clinically significant prior allergies to pegaspargase are eligible if Erwinia L-asparaginase can be substituted
  • Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective birth control method
  • Patients must not have received any prior re-induction attempts and must not have received treatment for prior extramedullary relapse; patients with primary induction failure are not eligible
  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: NCT00873093

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Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Terzah Horton, MD PhD Children's Oncology Group
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00873093     History of Changes
Other Study ID Numbers: NCI-2011-01908
NCI-2011-01908 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AALL07P1 ( Other Identifier: Children's Oncology Group )
AALL07P1 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
Study First Received: March 31, 2009
Results First Received: February 9, 2016
Last Updated: November 30, 2016

Additional relevant MeSH terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Methotrexate
Cytarabine
Liposomal doxorubicin
Etoposide phosphate
Pegaspargase
Doxorubicin
Prednisone
Bortezomib
Etoposide
Vincristine
Asparaginase
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Levoleucovorin
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 17, 2017