Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory Follicular Lymphoma
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Bortezomib in Combination With Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (VR-FND) for Relapsed or Refractory Follicular Lymphoma|
- Complete and Partial Response [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Complete Response: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms and normalization of biochemical abnormalities (eg. LDH) definitely assignable to follicular lymphoma.
Partial Response requires the following:
- greater than or equal to 50% decrease in the SPD of the 6 largest dominant nodes of nodal masses.
- No increase in size of other nodes, liver, or spleen.
- Splenic and hepatic nodes must regress by at least 50% in sum of the products (SPD).
- Bone marrow assessment in irrelevant for determination of Partial Response since it is not measurable disease; however, if positive the type of cell should be reported.
- No new lesions.
- Duration of Response [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]Duration of response is measured from time of treatment to time of disease progression
- Percentage of Subjects Experiencing Progression Free Survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]Progression free survival is measured from treatment to progression or death, whichever comes first. Progressive disease is measured as: 50% or greater increase from nadir in the sum of the products (SPD) of any previously identified abnormal node and the appearance of any new lesions during or at the end of treatment.
- Percentage of Subjects Experiencing Overall Survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]Overall survival is from the day of enrollment to date of death from any cause.
- Number of Participants With a Grade 3-4 Hematologic Toxicity. [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).
- Number of Participants With Neuropathy, Any Grade [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).
|Study Start Date:||January 2007|
|Study Completion Date:||September 2013|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Bortezomib (VELCADER) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.
Each cycle will be repeated every 28 days for 8 cycles maximum.
Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle
Other Name: VelcadeDrug: Rituximab
Rituximab 375 mg/m2 IV on day 1Drug: Fludarabine
Fludarabine 25 mg/m2 IV on days 1,2,3Drug: Mitoxantrone
Mitoxantrone 10 mg/m2 IV on day 2
Other Name: NovantroneDrug: Dexamethasone
Dexamethasone 20 mg orally on days 1,2,3,4,5
This is a phase II study using the combination of bortezomib, rituximab, fludarabine, mitoxantrone and dexamethasone. The combination will given over a 28 day cycle. In addition each patient will receive Pneumocystis carinii Pneumonia (PCP) prophylaxis with Trimethoprim/sulfamethoxazole (TMP/Sulfa) or equivalent agent. On day 4 the physician has the option of starting granulocyte colony-stimulating factor (GCSF), granulocyte macrophage colony-stimulating factor (GMCSF), or pegylated GCSF.
All patients who receive at least one dose of the drug will be evaluated for toxicity. Patients will be treated with the agent for at least 2 cycles to be considered eligible for evaluation of response. The chemotherapy dosing will continue until there is evidence of disease progression, a second recurrence of unacceptable toxicity, or a maximum of 8 courses of therapy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00510887
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David A Rizzieri, MD||Duke University|