Ofatumumab (O) in Combination With Chemotherapy: Hyper-Fractionated Cyclophosphamide, Doxorubicin, Vincristine and Dexamethasone (O-HyperCVAD) Alternating With Ofatumumab High-Dose Cytarabine and Methotrexate (O-MA) for Patients With Newly Diagnosed Mantle Cell Lymphoma
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
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
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,
V. To correlate surface CD20 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 C3, C4, and CH50 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.
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
All courses repeat every 21 days in the absence of disease progression or unacceptable
Eligible patients then undergo standard high dose chemotherapy and autologous stem cell
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Proportion of patients experiencing a complete response
Evaluated according to the International Working Group Response criteria as reported by Cheson et al. and the revised Cheson criteria.
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Weill Medical College of Cornell University||New York, New York 10021|