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
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01527149|
Recruitment Status : Active, not recruiting
First Posted : February 6, 2012
Results First Posted : June 23, 2020
Last Update Posted : March 18, 2022
|Condition or disease||Intervention/treatment||Phase|
|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||Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Methotrexate Biological: Ofatumumab Drug: Vincristine Sulfate||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||37 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||December 6, 2011|
|Actual Primary Completion Date :||April 26, 2018|
|Estimated Study Completion Date :||February 8, 2023|
Experimental: Treatment (monoclonal antibody and combination chemotherapy)
COURSES 1, 3, and 5 (O-HyperCVAD): Patients receive ofatumumab 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 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.
All courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Eligible patients then undergo standard HDC-ASCT.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous HDC-ASCT
Other Name: Autologous Stem Cell Transplantation
Given IV or PO
Drug: Doxorubicin Hydrochloride
Other: Laboratory Biomarker Analysis
Drug: Vincristine Sulfate
- Proportion of Patients Experiencing a Complete Response [ Time Frame: 22 weeks ]
Evaluated according to the International Working Group Response criteria as reported by Cheson et al. and the revised Cheson criteria.
Complete response is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Typically FDG-avid lymphoma: in patients with PET scan positive before therapy, a posttreatment residual mass of any size is permitted as long as it is PET negative. Variably FDG-avid lymphomas/FDG avidity unknown: in patients with a negative pretreatment PET scan, all lymph nodes and nodal masses must have regressed on CT to normal size (1.5 cm in their greatest transverse diameter for nodes 1.5 cm before therapy). Previously involved nodes that were 1.1 cm to 1.5 cm in their long axis and more than 1)
- Percentage of Participants With Autologous Stem Cell Transplantation [ Time Frame: Up to 6 weeks after the last dose of ofatumumab-chemotherapy, an average of 4 month ]Estimated using simple relative frequencies. The corresponding 95% confidence intervals will be computed using the method proposed in Clopper and Pearson.
- Change From Baseline in Percentage of Cells Positive for Ki67 [ Time Frame: Baseline and up to 3 years ]Mean change from baseline in Percentage of Cells Positive for Ki67 by patient response.
- Median of Serum Complement CD20 Levels [ Time Frame: Baseline ]Median serum C20 MFI (mean fluorescence intensity)
- Number of Participants With at Least One Serious Adverse Event [ Time Frame: Up to 3 years ]Evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
- Minimal Residual Disease (MRD) in Peripheral Blood Samples [ Time Frame: Up to 3 years ]Minimal residual disease (MRD) in peripheral blood samples at baseline.
- Minimal Residual Disease (MRD) in Bone Marrow Biopsy/Aspiration Samples [ Time Frame: Up to 3 years ]Minimal residual disease (MRD) in and bone marrow biopsy/aspiration samples at baseline.
- Median Overall Survival (OS) [ Time Frame: From baseline through study completion, an average of 5 years ]Estimated distributions obtained using the Kaplan-Meier method. Estimates of quantities such as median survival will be obtained. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed.
- Median Progression-free Survival (PFS) [ Time Frame: From baseline through study completion, an average of 5 years ]Estimated distributions obtained using the Kaplan-Meier method. Estimates of quantities such as median survival will be obtained. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed.
- Proliferation Signature Using Quantitative Real-time RT-PCR [ Time Frame: Baseline ]Relationship between proliferation signature and clinical outcome will be compared using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses.
- Proportion of Patients Who Experience Complete Remission as Assessed by HSFCM [ Time Frame: Up to 3 years ]Established when all CR criteria are met and negative flow cytometry examination of peripheral blood and bone marrow biopsy/aspiration collected at baseline, before courses 3 and 5, within 3 weeks after course 6, on day 100 (if HDC-ASCT eligible), and then every 6 months for 3 years.
- Time-to-tumor Progression (TTP) at 3 Years [ Time Frame: From baseline until objective tumor progression, as assessed up to 3 years ]Estimated percentage of patients that progressed at 3 years. Time to Progression distributions obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01527149
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Francisco Hernandez-ILizaliturri||Roswell Park Cancer Institute|