Clinical Trial: Intensive Induction Therapy Followed by High Dose Chemo and BM Transplant for Mantle Cell Lymphoma
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Intensive Induction Therapy Followed by Early High Dose Chemotherapy and Bone Marrow Transplantation for Mantle Cell Lymphoma
Brief Summary: Patients with mantle cell lymphoma have a grave prognosis. They usually have an initial response to therapy, however progress early in the course of the disease and have very poor survival. We hypothesize that the emergence of drug resistance is responsible for this early failure of therapy and therefore intensive therapy at induction followed by high dose therapy immediately may produce a better outcome.
Detailed Summary: Subjects will undergo an induction regimen consisting of 1 cycle of cytarabine (3 gm/m2 Intravenously over 1 hour every 12 hours for 8 total doses) and mitoxantrone (10 mg/m2/d intravenously [IV] over 30 minutes daily on days 1, 2, and 3). This will be combined with Alemtuzumab (anti-CD52 antibody) for 6-8 weeks. If, after this one cycle, subjects have not had progression of disease as noted on physical exam or radiographic scans, they will proceed to stem cell mobilization with cyclophosphamide. This will be immediately followed by high dose therapy with stem cell support. Following count recovery, rituximab will be used for 8 total doses as consolidation therapy. Involved field irradiation may be given post-transplant to those with localized bulky disease as well. Day -6: Carmustine (BCNU): 15 mg/kg (or 550 mg/m2) IV over 2 hrs. Day -4: Etoposide Day -2: Cyclophosphamide 100 mg/kg in 1 liter D5W over 2 hours.
Sponsor: Duke University
Current Primary Outcome:
- Disease Free Survival (DFS) [ Time Frame: 1 year ]
Number of patients who did not have documented recurrence for at 1 year after bone marrow transplantation.
We would like to detect an improvement over 0.25 in DFS at one year. Thirty (30) patients will be accrued and complete the transplant phase of therapy. We anticipate only 50% of patients enrolling to complete transplant, noting that approximately 60 patients total will need to be accrued. With 30 patients we can detect an improvement as small as 17% in magnitude, i.e., from an assumed 1-year DFS of 25% to a 1-year DFS of 42% with approximately 80% power. This is based on a one-sided test of hypothesis, testing at significance level 0.05 and the assumption that the true underlying 1-year DFS is 0.25. Greater differences in DFS are expected. If the 1-year DFS with the new treatment is greater than 42% the power is increased.
- Progression Free Survival (PFS) [ Time Frame: 1 year ]The number of patients who did not have disease progression, recurrence or die for 1 year after bone marrow transplantation.
Original Primary Outcome: Evaluate the efficacy in terms of duration of response of intensive induction therapy followed by high dose ablative therapy with autologous progenitor cell support [ Time Frame: 2 years ]
Current Secondary Outcome:
- Response to the induction regimen [ Time Frame: 12 weeks ]
Number of patients who respond to transplant. Complete Response (CR): No measurable disease. Remission must last for more than 4 weeks.
Complete Response with Residual Abnormality: CR with persistent mass in the mediastinum or abdomen that has regressed >50% following therapy and then stabilized with NO change over the rest of therapy.
Partial Response (PR): Reduction of >50% in the sum of the products of the perpendicular diameters of all measurable lesions lasting more than 4 weeks. Disappearance of constitutional symptoms must occur. >30% reduction in extension of the liver below the costal margin at the midclavicular line and the xiphoid process and normalization of liver function tests.
Stable Disease (SD): < 50% decrease or < 25% increase in the sum of the perpendicular diameters of measurable lesions and no new lesions.
Progressive Disease (PD): >= 25% increase in the product of the perpendicular diameters of any lesion or new areas of malignant disease.
- Response to the transplant phase of therapy [ Time Frame: 2 years ]
Number of patients who respond to transplant. Complete Response (CR): No measurable disease. Remission must last for more than 4 weeks.
Complete Response with Residual Abnormality: CR with persistent mass in the mediastinum or abdomen that has regressed >50% following therapy and then stabilized with NO change over the rest of therapy.
Partial Response (PR): Reduction of >50% in the sum of the products of the perpendicular diameters of all measurable lesions lasting more than 4 weeks. Disappearance of constitutional symptoms must occur. >30% reduction in extension of the liver below the costal margin at the midclavicular line and the xiphoid process and normalization of liver function tests.
Stable Disease (SD): < 50% decrease or < 25% increase in the sum of the perpendicular diameters of measurable lesions and no new lesions.
Progressive Disease (PD): >= 25% increase in the product of the perpendicular diameters of any lesion or new areas of malignant disease.
- Toxicity of the trial [ Time Frame: 2 years ]Number of grade 3 or higher events related to study treatment. Toxicities were assessed using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 2.0.
- Overall Survival (OS) [ Time Frame: 5 years ]Number of years patients survived after bone marrow transplantation
Original Secondary Outcome:
- Assess the response to the induction regimen [ Time Frame: 2 years ]
- Assess response to the transplant phase of therapy [ Time Frame: 2 years ]
- Monitor toxicity of the trial [ Time Frame: 2 years ]
Information By: Duke University
Dates:
Date Received: December 21, 2007
Date Started: February 1998
Date Completion:
Last Updated: July 16, 2014
Last Verified: July 2014
