Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT02073097|
Recruitment Status : Recruiting
First Posted : February 27, 2014
Last Update Posted : March 23, 2021
|Condition or disease||Intervention/treatment||Phase|
|Contiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma||Drug: Carfilzomib Biological: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin hydrochloride Drug: Vincristine sulfate Drug: Prednisone Drug: Pegfilgrastim Drug: Acyclovir||Phase 1 Phase 2|
I. To determine the safety of carfilzomib in combination with rituximab-cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) (CR-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and identify a recommended phase II dose (RP2D). (Phase I)
I. To determine if CR-CHOP improves the rates of 1-year progression free survival (PFS) and overall survival (OS) in non-germinal center (non-GC) DLBCL patients relative to historical controls treated with R-CHOP(Phase II) II. To determine response rates (complete and partial remission) in non-GC DLBCL patients treated with CR-CHOP and compare to historical controls treated with R-CHOP.
III. Because a proportion (~10%) of patients classified as non-GC by immunohistochemical (IHC) algorithms may not have the activated B-cells (ABC) subtyped of DLBCL, an exploratory secondary objective will compare the PFS, OS and response rates of the ABC subgroup of patients with DLBCL as determined by the Gene Expression Profiling with those of the overall group of non-GC DLBCL.
OUTLINE: This is a phase I, dose-escalation study of carfilzomib followed by a phase II study.
Patients receive rituximab intravenously (IV) over at least 90 minutes, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 3-5 minutes, vincristine sulfate IV over 1 minute on day 1, and prednisone orally (PO) on days 1-5. Patients also receive carfilzomib IV over 30 minutes on days 1, 2, 8 and 9. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and at 6, 12, and 24 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Carfilzomib in Combination With R-CHOP (CR-CHOP) for Patients With Diffuse Large B-cell Lymphoma|
|Actual Study Start Date :||October 1, 2014|
|Estimated Primary Completion Date :||August 2021|
|Estimated Study Completion Date :||September 2021|
Experimental: rituximab, combination chemotherapy, carfilzomib
Participants receive (every 21 day cycle):
Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Given IV, according to dose level. Cohorts begin with dose level (DL)1, escalated in standard 3+3 design to identify a recommended phase 2 dose DL (-2) 11 mg/m2 on day 1 and 2 every 21 days, cycles 1-6
DL (-1) 15 mg/m2 on days 1 and 2 every 21 days, cycles 1-6
DL (1) 20 mg/m2 days 1,2 every 21 days, cycles 1-6
DL (2) 20 mg/m2 days 1,2 of cycle 1 followed by 27 mg/m2 days 1,2 every 21 days for cycles 2-6.
DL (3) 20 mg/m2 days 1,2 of cycle 1 followed by 36 mg/m2 days 1,2 every 21 days for cycles 2-6.
DL(4) 20 mg/m2 days 1,2 of cycle 1 followed by 45 mg/m2 days 1,2 every 21 days for cycles 2-6
DL (5) 20 mg/m2 days 1,2 of cycle 1 followed by 56 mg/m2 days 1,2 every 21 days for cycles 2-6
Given IV (375mg/m^2)
Given IV (750mg/m^2)
Drug: Doxorubicin hydrochloride
Given IV (50mg/m^2)
Drug: Vincristine sulfate
Given IV (1.4mg/m^2)
Given PO (100mg)
6 mg SC day 4 (every 21 days). Filgrastim 300 or 480 mcg IV/SC daily days 1-10 may be substituted if pegfilgrastim is not available. ONPROTM is also an acceptable method of administration.
Other Name: Zovirax
- Recommended Phase II dose (Phase I) [ Time Frame: 21 days ]Highest dose administered when no more than 1 out of 6 patients experience lose limiting toxicity below the maximally administered dose.
- Progression Free Survival (Phase II) [ Time Frame: 30 days after treatment ]The number of days until Progression-free Survival (PFS) when PFS is defined as the time from entry onto study until lymphoma progression or death from any cause. PFS will be estimated using a Kaplan-Meier curve.
- Overall Survival (Phase II) [ Time Frame: 30 days after treatment ]The number of days patients are alive from entry onto study until lymphoma progression or death from any cause. Overall survival will be estimated with a Kaplan-Meier curve
- Complete Response Rate (Phase II) [ Time Frame: 30 days after treatment ]The number of patients with a complete response as defined by a complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy
- Partial Response Rate (Phase II) [ Time Frame: 30 days after treatment ]The number of patients with a partial response as defined a >50% decrease in the sum of the product of the diameter of up to six of the largest nodes; no increase in the any node, liver, or spleen; no new sites of disease.
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): NCT02073097
|Contact: Brian Hill, MD, PhD||1-866-223-8100||TaussigResearch@ccf.org|
|United States, Georgia|
|Winship Cancer Institute, Emory University||Withdrawn|
|Atlanta, Georgia, United States, 30322|
|United States, New York|
|Roswell Park Comprehensive Cancer Center||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Pallawi Torka, MD|
|United States, Ohio|
|University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Paolo Caimi, MD 800-641-2422 CTUReferral@UHhospitals.org|
|Principal Investigator: Paolo Caimi, MD|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Brian T. Hill, MD, PhD 866-223-8100 TaussigResearch@ccf.org|
|Principal Investigator: Brian T. Hill, MD, PhD|
|Principal Investigator:||Brian Hill, MD, PhD||Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center|