Four Drug Reinduction With Bortezomib for Relapsed or Refractory ALL or LL in Children and Young Adults
Condition: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Velcade; Methotrexate; Methotrexate / Hydrocortisone / Cytarabine; Dexamethasone; Mitoxantrone; Vincristine; Pegaspargase
Intervention description: 4 doses of study drug will be given.; Intrathecal dose For CNS negative patients, Day 1 and Day 8; Intrathecal dose for CNS positive patients, Day 1, 8, 15, 22; Days 1-5 and 15-19; Days 1 and 2; Days 1, 8, 15, 22; Days 3 and 17
Intervention MeSH terms: Cytarabine; Dexamethasone; Hydrocortisone; Methotrexate; Vincristine; Bortezomib; Mitoxantrone; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 1 Year
Maximum age: 39 Years
Healthy volunteers: No
Keywords: Relapsed, Refractory

Summary:

      This is a phase II study designed to investigate the combination of bortezomib with the
      mitoxantrone reinduction regimen used in the ALL R3 trial. The study will enroll patients
      with high risk ALL relapse including early bone marrow relapse and second or greater relapse
      of any kind. Patients with relapsed LL will also be eligible. Bone marrow evaluation will be
      performed after blood counts recover to assess the rate of CR (<5% bone marrow blasts) and
      MRD status in children following this regimen. Further treatment with or without HSCT will be
      at the discretion of the primary physician.
    

Eligibility criteria:

        Inclusion Eligibility Criteria

          -  Age: > 1 and < 40 years of age at the time of enrollment

          -  Diagnosis: Precursor B-cell ALL with bone marrow (BM) or combined BM/extramedullary
             relapse; T-cell ALL with relapsed disease; LL with relapsed disease, or ALL(T or
             pre-B) with primary refractory disease after at least two regimens

          -  Performance Score: 50% for patients

          -  Prior Therapy 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. In addition, the following requirements must be
        met:

        Cytotoxic therapy: 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.

        Biologic (anti-neoplastic) agent: At least 7 days since the completion of therapy with a
        biologic agent or donor lymphocyte infusions (DLI).

        Stem cell transplant or rescue: No evidence of active graft-vs-host disease (GVHD) and ≥ 4
        months must have elapsed from time of transplant. Must not be receiving GVHD prophylaxis.

          -  Adequate Organ Function Requirements

          -  Reproductive Function: Female patients of childbearing potential must have a negative
             pregnancy test confirmed within 2 weeks prior to enrollment, must agree not to
             breastfeed their infants while on this study.Male and female patients of child-bearing
             potential must agree to use 2 effective methods of contraception approved by the
             investigator, at the same time, from the time of signing the informed consent form and
             for a minimum of 6 months after study treatment, or agree to completely abstain from
             heterosexual intercourse.

          -  Signed written informed consent. Assent from children will be obtained per
             institutional guidance.

        Exclusion Eligibility Criteria

          -  known allergy to any of the drugs on the study with the exception of PEG-asparaginase

          -  Isolated CNS or isolated testicular disease

          -  Systemic fungal, bacterial, viral or other infection that is exhibiting ongoing
             signs/symptoms related to the infection without improvement despite appropriate
             antibiotics or other treatment. The patient needs to be off pressors and have negative
             blood cultures for 48 hours.

          -  Known optic nerve and/or retinal involvement

          -  Patients with concomitant genetic syndrome

          -  Cumulative prior anthracycline exposure must not exceed 400 mg/m2

          -  Patients who have previously received bortezomib or other proteasome inhibitors

          -  Patients taking anticonvulsants known to activate the cytochrome p450 system

          -  Patients who cannot receive any asparaginase products

          -  Patients who are pregnant or breast-feeding

          -  Patients with planned non-protocol chemotherapy, radiation therapy, or immunotherapy
             during the study period.

          -  Significant concurrent disease, illness, psychiatric disorder or social issue that
             would compromise patient safety or compliance with the protocol treatment or
             procedures, interfere with consent, study participation, follow up, or interpretation
             of study results.

          -  Patients with myocardial infarction within 6 months prior to enrollment or has New
             York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina,
             severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities.

          -  Diagnosed or treated for another malignancy within 2 years of enrollment

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and throughout the duration of
             this trial.Radiation therapy within 3 weeks before randomization.