A Phase I/II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituxamib, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL) (PILS-2)
This study has been terminated.
(The Principal Investigator left Columbia University and chose not to re-initiate the study at new facility)
Information provided by (Responsible Party):
Owen A. O'Connor, Columbia University
First received: March 9, 2009
Last updated: July 29, 2013
Last verified: July 2013
The proteasome inhibitor Bortezomib in combination with Rituximab, Cyclophosphamide and Prednisone will increase progression free survival, event free survival and overall survival of patients in with relapsed/refractory indolent B cell lymphoproliferative disorders and Mantle Cell Lymphoma (MCL).
Follicular Lymphoma (Grade I, II, III)
B-Cell Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia
Marginal Zone Lymphoma
Mantle Cell Lymphoma
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase I/II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituxamib, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL)
Primary Outcome Measures:
- Phase I: Maximum Tolerated Dose [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Phase II: To determine the frequency and duration of complete and partial responses [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
| Study Start Date:
| Estimated Study Completion Date:
| Primary Completion Date:
||December 2012 (Final data collection date for primary outcome measure)
Bortezomib in combination with rituximab, cyclophosphamide, and prednisone
Cohort 1: Weekly dosing, the planned dose escalation will begin with bortezomib at 1.3 mg/m2 and 750 mg/m2 of cyclophosphamide and not exceed 1.8 mg/m2 of bortezomib and 1000 mg/m2 of cyclophosphamide. Rituxamib, 375 mg/m2 and prednisone 100 mg/day remain constant.
Cohort 2: Twice weekly dosing: the planned dose escalation will begin with 1.0 mg/m2 bortezomib and 750 mg/m2 cyclophosphamide and not exceed 1.5 mg/m2 bortezomib and 1000 mg/m2 cyclophosphamide. Rituxamib 375 mg/m2 and prednisone 100 mg/day remain constant.
This is a Phase I/II study to evaluate the safety and efficacy of bortezomib for patients with indolent and mantle cell lymphomas. The primary objective in Phase I is to determine the maximum tolerated dose (MTD) of bortezomib when given in combination with rituximab, cyclophosphamide, and prednisone (RCP). The primary objective in Phase II is to determine the frequency and duration of complete and partial responses in patients treated with bortezomib + RCP (RCB or P) administered every 21 days for a total of 68 cycles.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patients must have histologically confirmed (using the WHO Classification): chronic lymphocytic leukemia/B cell small lymphocytic lymphoma, any marginal zone lymphoma, follicular lymphoma, grade I, II, III, Waldenstrom's macroglobulinemia (all in cohort 1 of the phase II portion of the study), or mantle cell lymphoma (cohort 2 of the phase II portion of the study). Patients with transformed indolent lymphomas will be enrolled on the phase I portion, but not the phase II portion of the study.
- For the phase I portion of this study, all patients must have assessable disease. For the phase II portion all NHL patients (except SLL/CLL and Waldenstrom's macroglobulinemia, discussed below) must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as >2 cm with conventional techniques or as >1 cm with spiral CT scan). Lymph nodes measuring < 1 cm in the short axis are considered normal. For chronic lymphocytic leukemia, patients must have an absolute lymphocytosis > 5 x 109/L with a B cell phenotype (CD19 or CD20 co expression with CD5, CD 23 +/), with > 30% bone marrow lymphocytes. Staging will be made according to the modified Rai as outlined.
- Patients must have received at least one but no more than three prior regimens of conventional cytotoxic therapy, and must be off all cytotoxic chemotherapy for at least four weeks prior to study enrollment (6 weeks for BCNU or mitomycin C, 12 weeks with recovery to baseline counts for radioimmunotherapy). Patients are allowed to have received one course of prior radioimmunotherapy (RIT: either tositumomab or ibritumomab). Prior recipients of stem cell transplantation will be included, with the preparative cytoreductive and high dose therapies counted collectively as one prior therapy.
- Patients must not have received any therapeutic monoclonal antibodies (e.g. rituximab, tositumomab, ibritumomab alemtuzumab, etc.) within 3 months of enrollment (except for patients enrolled on the phase I portion, who may have received rituximab up to 7 days prior to enrollment). Patients who have been treated with monoclonal antibodies within 3 months may be enrolled if they show progression of disease on this therapy, as long as they have not received the treatment within 7 days of enrollment.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of bortezomib in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single agent trials, if applicable.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C, 12 weeks or lack of recovery to baseline counts for RIT) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients who have received a therapeutic monoclonal antibody within 3 months (except those with objective evidence of PD).
- Patients may not be receiving any other investigational agents.
- Patients with known brain metastases or meningeal disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Patients who have had any major surgery within four weeks of study entry.
- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, cerebrovascular accident (CVA) or transient ischemic attack within 6 months of study enrollment, unstable angina pectoris, cardiac arrhythmia, EKG evidence of acute ischemia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because bortezomib is a novel agent that may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bortezomib, breastfeeding should be discontinued if the mother is treated with this agent.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00859443
|Columbia University Medical Center
|New York, New York, United States, 10032 |
||Owen A O'Connor, MD, PhD
No publications provided
||Owen A. O'Connor, Assistant Professor of Clinical Medicine, Columbia University
History of Changes
|Other Study ID Numbers:
|Study First Received:
||March 9, 2009
||July 29, 2013
||United States: Institutional Review Board
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 12, 2013
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Immune System Diseases
Neoplasms, Plasma Cell
Blood Protein Disorders