Carfilzomib and Hyper-CVAD in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoma
Condition: Contiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial studies the side effects and best dose of carfilzomib when given together
      with the hyperfractionated (hyper)-cyclophosphamide, vincristine sulfate, doxorubicin
      hydrochloride, and dexamethasone (CVAD) chemotherapy regimen in treating patients with newly
      diagnosed acute lymphoblastic leukemia or lymphoma. Carfilzomib may stop the growth of cancer
      cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy,
      such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone,
      work in different ways to stop the growth of cancer cells, either by killing the cells, by
      stopping them from dividing, or by stopping them from spreading. Giving carfilzomib with
      combination chemotherapy may kill more cancer cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Safety and tolerability of administering carfilzomib in combination with hyper-CVAD
      chemotherapy.

      II. Recommended dose of carfilzomib in combination with hyper-CVAD chemotherapy for the
      future phase II trial.

      SECONDARY OBJECTIVES:

      I. Rate of remission after 2nd and 4th cycles. II. Incidence of minimal residual disease by
      flow cytometry at 4th cycle.

      OUTLINE: This is a dose escalation study of carfilzomib.

      Patients receive carfilzomib intravenously (IV) over 30 minutes on days 0, 1, 7, and 8.
      Patients also receive hyper-CVAD comprising cyclophosphamide IV over 2 hours every 12 hours
      for 6 doses beginning on day 1, vincristine sulfate IV on days 4 and 11, doxorubicin
      hydrochloride IV over 2-24 hours on day 4, and dexamethasone orally (PO) on days 1-4 and
      11-14 (courses 1 and 3) and methotrexate IV over 24 hours on day 1, cytarabine IV over 2
      hours every 12 hours for 4 doses starting on day 2, leucovorin calcium IV or PO every 6 hours
      beginning 36 hours after the start of methotrexate infusion, and methylprednisolone IV every
      12 hours for 6 doses beginning on day 1 (courses 2 and 4). Patients with cluster of
      differentiation (CD)20 positive disease also receive rituximab twice daily on days 1 and 11
      of courses 1 and 3 and days 1 and 8 of courses 2 and 4. Treatment repeats every 3-4 weeks for
      4 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 28 days.
    

Intervention name(s): carfilzomib; cyclophosphamide; vincristine sulfate; doxorubicin hydrochloride; dexamethasone; methotrexate; cytarabine; leucovorin calcium; methylprednisolone; rituximab; laboratory biomarker analysis
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Biological; Other
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given PO; Given IV; Given IV; Given IV or PO; Given IV; Correlative studies
Other intervention name(s): Kyprolis; PR-171; CPM; CTX; Cytoxan; Endoxan; Endoxana; leurocristine sulfate; VCR; Vincasar PFS; ADM; ADR; Adria; Aeroseb-Dex; Decaderm; Decadron; DM; DXM; amethopterin; Folex; methylaminopterin; Mexate; MTX; ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; CF; CFR; LV; Depo-Medrol; Medrol; MePRDL; Solu-Medrol; Wyacort; IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Prednisolone hemisuccinate; Prednisolone phosphate; Levoleucovorin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment