Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Condition: 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
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Recurrence
Intervention: L-asparaginase; doxorubicin hydrochloride; therapeutic hydrocortisone; vincristine sulfate; cytarabine; prednisone; bortezomib; pegaspargase; methotrexate; etoposide phosphate; cyclophosphamide; filgrastim; leucovorin calcium; laboratory biomarker analysis; High Dose MTX
Intervention description: Given IM 6000 IU/m2/dose Days 2 and 9; Given IV 60 mg/m2/dose on Day 1; Given IT (8mg - 15mg) Age-based dosing Block 1: Days 8,15, 22 and 29 Block 2: Days 1 and 22; Given IV 1.5 mg/m2 (max 2 mg) on Days 1, 8, 15 and 22; Given IT or IV 3,000 mg/m2/dose on Days 1, 2, 8 and 9; Given PO or IV 40 mg/m2/day on Days 1-28; Given IV 1.3 mg/m2/dose Block 1: Days 1, 4, 8 and 11 Block 2: Days 1, 4 and 8; Given IM or IV (over 2 hours) 2500 IU/m2/dose on days 2, 8,15 and 22; Given IT (8mg - 15mg) Age-based dosing Block 1: Days 15 and 29 Block 2: Days 1 and 22; Given IV 100 mg/m2/dose on Days 1-5; Given IV 440 mg/m2/dose on Days 1-5; Given IV or SC 5 micrograms/kg/dose Only on Day 6; Given PO or IV 15mg/m2/dose q6h x 3 doses; Correlative studies; IV 5000 mg/m2/dose Block 2: Day 22
Intervention MeSH terms: Leucovorin; Cytarabine; Prednisone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Bortezomib; Asparaginase; Pegaspargase; Etoposide phosphate; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 148.0
Sex: All
Minimum age: 1 Year
Maximum age: 31 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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