Bortezomib, Rituximab and Combination Chemotherapy in Treating Participants With Mantle Cell Lymphoma
Condition: Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This phase I/II trial studies the side effects and best dose of bortezomib when given with
      rituximab and chemotherapy drugs and to see how well they work in treating participants with
      mantle cell lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the
      enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with
      the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as
      cyclophosphamide, doxorubicin, vincristine, dexamethasone, methotrexate, and cytarabine, 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 bortezomib, rituximab
      and combination chemotherapy may work better at treating mantle cell lymphoma.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Determine the safety and the maximum tolerated dose (MTD) of bortezomib when added to the
      combination of rituximab, methotrexate, and cytarabine alternating with bortezomib,
      rituximab-hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone
      (hyperCVAD) in patients with untreated aggressive mantle cell lymphoma. (Phase I) II.
      Evaluate the time to failure (TTF) rate following therapy with bortezomib plus
      rituximab-hyperCVAD alternating with bortezomib plus rituximab-high dose
      methotrexate/cytarabine in patients between 18 and 79 years of age with untreated aggressive
      mantle cell lymphoma. (Phase II)

      SECONDARY OBJECTIVES:

      I. Evaluate overall response rate, complete remission rate, overall survival, and duration of
      remission. (Phase I) II. Evaluate overall response rate, overall survival, and duration of
      remission. (Phase II) III. Evaluate toxicity of the combination regimen. (Phase II) IV.
      Correlate outcome with pretreatment markers. (Phase II)

      OUTLINE: This is a phase I, dose-escalation study of bortezomib followed by a phase II study.

      Participants receive Drug Combination I during courses 1, 3, 5, and 7 (if needed) and Drug
      Combination II during courses 2, 4, 6, and 8 (if needed) in the absence of disease
      progression or unacceptable toxicity.

      Drug Combination I: Participants receive rituximab intravenously (IV) over 6 hours on day 1,
      cyclophosphamide IV over 3 hours twice daily (BID) on days 2-4, doxorubicin IV over 15-30
      minutes on day 5, vincristine IV over 15-30 minutes on days 5 and 12, dexamethasone orally
      (PO) or IV on days 2-5 and 12-15, and bortezomib IV over a few seconds after the first dose
      of cyclophosphamide and immediately after vincristine and doxorubicin have been given on day
      5.

      Drug Combination II: Participants receive rituximab IV over 6 hours on day 1, methotrexate IV
      over 24 hours on day 2, and cytarabine IV over 2 hours every 12 hours on days 3-4.

      After completion of study treatment, participants are followed up every 3 months for 1 year,
      every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.
    

Intervention name(s): Bortezomib; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Methotrexate; Rituximab; Vincristine
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Biological; Drug
Intervention description(s): Given IV; Given IV; Given IV; Given PO or IV; Given IV; Given IV; Given IV; Given IV
Other intervention name(s): [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; LDP 341; MLN341; PS-341; PS341; Velcade; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; Visumetazone; Adriablastin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituxan; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; RTXM83; LEUROCRISTINE; VCR; Vincrystine
Intervention MeSH terms: Cytarabine; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Bortezomib; Daunorubicin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; BB 1101
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment