A Phase 1, Open-label Trial of Oral Azacitidine (CC-486) Plus RCHOP in Subjects With Large B-Cell Lymphoma or Follicular Lymphoma or Transformed Lymphoma
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|ClinicalTrials.gov Identifier: NCT02343536|
Recruitment Status : Completed
First Posted : January 22, 2015
Last Update Posted : August 28, 2020
The goal of the study is to identify a dose and schedule of CC-486 that can be safely administered with R-CHOP. To evaluate the safety and maximum tolerated dose (MTD) or the maximal administered dose (MAD) of CC-486 in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in subjects with high risk (IPI 2 or more) previously untreated DLBCL or Grade 3B FL.
Also, to determine pharmacokinetics (PK) of CC-486 when administered alone and in combination with R-CHOP and to explore preliminary efficacy of CC-486 plus R-CHOP by 2007 International Working Group (IWG) criteria.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma, Large B-Cell, Diffuse Lymphoma, Follicular||Drug: Oral Azacitidine Drug: Rituximab Drug: cyclophosphamide Drug: Vincristine Drug: Prednisone||Phase 1|
Expanded Access : An investigational treatment associated with this study has been approved for sale to the public. More info ...
The purpose of this study is to evaluate the safety of oral azacitidine (CC-486) when combined with R-CHOP (the treatment regimen normally used in treating Diffuse large B-cell lymphoma or Grade 3B follicular lymphoma). This study also proposes to explore the pharmacokinetics of oral azacitidine when administered in combination with R-CHOP and to assess the effects the drug can have on the human body, as well as the ability of CC 486 in combination with R CHOP to further effect the response of tumors associated with Diffuse large B-cell lymphoma or Grade 3B follicular lymphoma, .
Oral azacitidine in combination with R-CHOP has not been approved for the treatment of Diffuse large B-cell lymphoma or Grade 3B follicular lymphoma and its use in this study is investigational. Various dose levels of this investigation treatment will be administered to subject enrolled into the study.
This study is separated into three periods: Screening and Registration, Treatment and Follow-up periods. Before the patient can receive the study drug the doctor will perform tests to find out whether he/she can participate in the study. This is done during the Screening Period. If the patient and the treating physician determine that the patient is eligible to participate in the study, the patient will be registered in the study and assigned to receive one of the investigational dose levels of oral azacitidine.
The Treatment period starts when the patient receives their first dose of the study drug. The maximum time the patient will receive study treatment is 5 months. The intent is for the patient to complete 6 cycles of treatment. Each cycle will be 21 days. The Follow-up period starts when the patient's treatment is completed or discontinued for any reason. The patient will have fewer exams, tests and visits once entering the follow-up period. These visits will be every 6 months for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||59 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-label, Multicenter Trial of Oral Azacitidine (CC-486) Plus R-CHOP in Subjects With High Risk (IPI 3 or More) Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3B Follicular Lymphoma.|
|Actual Study Start Date :||April 29, 2015|
|Actual Primary Completion Date :||January 29, 2020|
|Actual Study Completion Date :||January 29, 2020|
Experimental: Oral Azacitidine (CC-486) and R-CHOP
Will examine four escalating dose-levels of CC- 486 (100 mg, 150 mg, 200 mg and 300 mg).
Drug: Oral Azacitidine
Other Name: CC-486
Active Comparator: R-CHOP
R-CHOP, (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) * rituximab, cyclophosphamide, doxorubicin, and vincristine are administered on Day 1; while prednisone is administered Days 1-5
- Maximum Tolerated Dose (MTD) [ Time Frame: 1 year ]The dose level corresponding to the target Dose Limiting Toxicity (DLT) probability of 0.20.
- Maximal Administered Dose (MAD) [ Time Frame: 1 Year ]The highest recorded dose administered to a subject if the MTD is not reached
- Adverse Event (AE) [ Time Frame: 2 Years ]Number of participants with adverse events
- Pharmacokinetics- Cmax [ Time Frame: 2 Years ]Maximum observed concentration in plasma
- Pharmacokinetics - AUC [ Time Frame: 2 Years ]Area under the concentration-time curve
- Pharmacokinetics - Tmax [ Time Frame: 2 Years ]Time to maximum concentration
- Pharmacokinetics - t1/2 [ Time Frame: 2 Years ]Terminal half-life
- Pharmacokinetics CL/F [ Time Frame: 2 Years ]Apparent total body clearance
- Pharmacokinetics - Vz/F [ Time Frame: 2 Years ]Apparent volume of distribution
- Overall response rate (ORR) [ Time Frame: 4 Years ]Efficacy evaluation of CC-486 plus R-CHOP of the percentage of subjects achieving and clinical response (Complete or Partial Remission) as assessed by 2007 International Working Group (IWG) criteria for non-Hodgkin lymphoma as evaluated by investigator review.
- Complete response (CR) rate [ Time Frame: 4 Years ]Efficacy evaluation of CC-486 plus R-CHOP of the percentage of subjects achieving Complete Remission as assessed by 2007 International Working Group (IWG) criteria for non-Hodgkin lymphoma as evaluated by investigator review.
- Progression free survival (PFS) [ Time Frame: 4 Years ]Efficacy evaluation of CC-486 plus R-CHOP. Progression-free survival is calculated as the time from C1D1 to the first documented progression or death due to any cause. Progression will be assessed by 2007 International Working Group (IWG) criteria for non-Hodgkin lymphoma as evaluated by investigator review.
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): NCT02343536
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02117|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Weill Cornell Medicine|
|New York, New York, United States, 10065|
|United States, Rhode Island|
|Rhode Island Hospital|
|Providence, Rhode Island, United States, 02903|
|Study Director:||Lei Zhang, MD||Celgene|