Ofatumumab in Combination With Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine Sulfate, and Dexamethasone Alternating With Ofatumumab in Combination With Cytarabine and Methotrexate in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma
Condition: Stage I Mantle Cell Lymphoma; Stage II Contiguous Mantle Cell Lymphoma; Stage II Non-Contiguous Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase II trial studies how well ofatumumab in combination with cyclophosphamide,
      doxorubicin hydrochloride, vincristine sulfate, and dexamethasone alternating with ofatumumab
      in combination with cytarabine and methotrexate works in treating patients with newly
      diagnosed mantle cell lymphoma (MCL). Monoclonal antibodies, such as ofatumumab, may
      interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy,
      such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, dexamethasone,
      cytarabine, and methotrexate, 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 ofatumumab together with alternating regimens of combination chemotherapy
      may kill more cancer cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To determine the overall response rate (ORR), and in particular, the complete remission
      rate (CRR) in previously untreated MCL treated with ofatumumab in combination with aggressive
      chemo-immunotherapy.

      SECONDARY OBJECTIVES:

      I. To determine the high sensitivity flow cytometry (HSFCM) complete remission rate
      (HSFCM-CRR) in previously untreated MCL treated with ofatumumab in combination with
      aggressive chemo-immunotherapy +/- high dose chemotherapy and autologous stem cell transplant
      (HDC-ASCT).

      II. To determine the time-to-progression (TTP), progression-free survival (PFS) and overall
      survival (OS) of patients with previously untreated MCL treated with ofatumumab and
      aggressive chemoimmunotherapy +/- HDC-ASCT.

      III. To determine the toxicity profiles of ofatumumab in combination with high dose
      cytarabine chemoimmunotherapy +/- HDC-ASCT.

      IV. To correlate minimal residual disease (MRD) at different time intervals with TTP, PFS,
      and OS.

      V. To correlate surface cluster of differentiation (CD)20 levels, Ki67, and additional
      cytogenetic abnormalities in pretreatment tumor biopsies with respect to ORR, CRR, TTP, PFS,
      or OS.

      VI. To determine the relationship between proliferation signature and clinical outcome using
      quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR).

      VII. To determine changes in surface CD20 levels, Ki67, or gain of additional cytogenetic
      abnormalities in relapsed/refractory tumor specimens.

      VIII. To correlate serum component (C)3, C4, and hemolytic complement (CH)50 levels measured
      at baseline and at the end of first ofatumumab infusion with ORR, CRR, median response rate
      (MRR), TTP, PFS and OS.

      IX. Evaluate the ability of the induction and consolidation therapy to get 70% of patients to
      autologous stem cell transplantation.

      X. Evaluate the tolerability and CD34+ cell yield following therapy with patient and
      hyper-fractionated cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and
      dexamethasone (HyperCVAD)/high-dose cytarabine and methotrexate (HD-MA).

      XI. To compare differences in response rate in patients with MCL treated with ofatumumab +
      HyperCVAD/HD-MA according Cheson and Modified Cheson Criteria.

      OUTLINE:

      COURSES 1, 3, and 5 (O-HyperCVAD): Patients receive ofatumumab intravenously (IV) on day 1,
      cyclophosphamide IV over 2 hours every 12 hours for 6 doses on days 3-5, doxorubicin
      hydrochloride IV continuously over 72 hours on days 6-8, vincristine sulfate IV on days 6 and
      13, and dexamethasone IV or orally (PO) on days 3-6 and 13-16.

      COURSES 2, 4, and 6 (O-HD-MA): Patients receive ofatumumab IV on day 1, methotrexate IV
      continuously over 24 hours on day 3, and cytarabine IV over 2 hours every 12 hours on days
      4-5.

      Treatment repeats every 21 days for 6* courses in the absence of disease progression or
      unacceptable toxicity.

      Eligible patients then undergo standard high dose chemotherapy and autologous stem cell
      transplant (HDC-ASCT). Patients achieving a high sensitivity flow cytometry complete
      remission (HSFCM-CR) after 2 courses may proceed to HDC-ASCT after completing 4 courses of
      treatment.

      After completion of study treatment, patients are followed up every 4 months for 2 years,
      every 6 months for 3 years, and then as clinically instructed.
    

Intervention name(s): Autologous Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Methotrexate; Ofatumumab; Vincristine Sulfate
Intervention type(s): Procedure; Drug; Drug; Drug; Drug; Other; Drug; Biological; Drug
Intervention description(s): Undergo autologous HDC-ASCT; Given IV; Given IV; Given IV or PO; Given IV; Correlative studies; Given IV; Given IV; Given IV
Other intervention name(s): Autologous Stem Cell Transplantation; (-)-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-Arabinofuranosylcytosine; 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; Cytosar-U; Cytosine 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; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; 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; Arzerra; GSK1841157; HuMax-CD20; HuMax-CD20, 2F2; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate
Intervention MeSH terms: Cytarabine; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Ofatumumab; Antibodies, Monoclonal; BB 1101
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment