|- candidate number||5636|
|- NTR Number||NTR1772|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||20-apr-2009|
|- Secondary IDs||2006-086 METC Erasmus MC|
|- Public Title||Bortezomib maintenance therapy in newly diagnosed patients with mantle cell lymphoma, responsive on rituximab combined with CHOP and high dose Ara-C and after BEAM with auto PSCT rescue.|
|- Scientific Title||Bortezomib maintenance therapy in newly diagnosed patients with mantle cell lymphoma, responsive on rituximab combined with CHOP and high dose Ara-C and after BEAM with auto PSCT rescue.|
|- ACRONYM||HOVON 75 MCL|
|- hypothesis||The objective of this phase II study is to determine whether there is an indication that bortezomib maintenance might result in a better event free survival. |
|- Healt Condition(s) or Problem(s) studied||Mantle cell lymphoma|
|- Inclusion criteria||1. Patients with histologically and immunologically proven diagnosis of MCL (WHO classification);|
2. Ann Arbor stage II ¨C IV;
3. CD20 positive;
4. Age 18 - 65 years (inclusive);
5. WHO performance ¡Ü 2;
6. Measurable disease (also patients with isolated bone marrow disease are accepted) (appendix B);
7. Written informed consent.
|- Exclusion criteria||1. Renal failure (creatinine clearance < 50 ml/min);|
2. Known hypersensitivity to murine antibodies, boron or mannitol;
3. Any other organ dysfunction or failure that may present a risk to the patient during any phase of protocol treatment;
4. Presence of CNS involvement by NHL;
5. Known HIV and hepatitis B or C seropositivity;
6. Pregnancy or lactation;
7. Prior treatment with chemotherapy, radiotherapy or immunotherapy for this lymphoma, except local radiotherapy in case of (potential) organ dysfunction by localized lymphoma mass or infiltration;
8. Other active malignancy (less than 5 years in complete remission) except skin (non-melanoma) or cervix carcinoma stage 1;
9. Active systemic infection requiring treatment;
10. Peripheral neuropathy or neuropathic pain Grade 2 or higher as defined by NCI CTCAE version 3;
11. Uncontrolled or severe cardiovascular disease, including MI within 6 months of enrolment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis;
12. Serious medical condition (such as severe hepatic impairment, pericardial disease, acute diffuse pulmonary disease, systemic infections etc) or psychiatric illness likely to interfere with participation in this clinical study.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mrt-2007|
|- planned closingdate||1-okt-2010|
|- Target number of participants||90|
|- Interventions||All registered patients will be treated with three courses of R-CHOP followed by two courses of HD Ara-C plus Rituximab. Patients with SD or PD (conventional criteria) after the second HD Ara-C course will go off study. Patients in CR or PR will continue with an autologous stem cell transplantation after BEAM conditioning. After this, patients will be randomized for treatment with bortezomib maintenance therapy or no further treatment, unless there is progression or relapse. |
|- Primary outcome||Event free survival (EFS).|
|- Secondary outcome||1. Residual disease (quality of remission) as measured with FDG-PET, flow cytometry and molecular studies;|
2. Toxicity of bortezomib maintenance therapy after high dose treatment;
3. Overall survival.
|- Timepoints||1. Event Free Survival: Hazard ratio and difference in 2 year EFS with 95% confidence intervals;|
2. Overall Survival: Hazard ratio and difference in 2 year OS with 95% confidence intervals;
3. Development of quantifiable residual disease, as assessed by FDG-PET, flow cytometry and molecular studies during bortezomib maintenance in comparison without further treatment.
|- Trial web site||www.hovon.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Dr. J.K. Doorduijn|
|- CONTACT for SCIENTIFIC QUERIES||Dr. J.K. Doorduijn|
|- Sponsor/Initiator ||HOVON Data Center|
(Source(s) of Monetary or Material Support)
|Amgen, Dutch Cancer Society, Roche Nederland BV, Johnson&Johnson-Orthobiotech, Novartis|
|- Brief summary||Study phase: II|
Primary objective:To study the efficacy and toxicity of bortezomib maintenance after induction with HD Ara-C and stem cell transplantation.
Secondary objective:To study the value of FDG-PET, flow cytometry and IGVH–PCR for defining the quality of remission after induction with high dose chemotherapy and Rituximab, after auto PSCT and during maintenance treatment with bortezomib, in comparison to conventional definitions.
Patients with newly diagnosed mantle cell lymphoma who reached PR or CR after chemotherapy combined with rituximab and high dose treatment followed by autologous stem cell transplantation.
Prospective, multicenter, phase II.
Duration of treatment:
Expected duration of induction, intensification and BEAM with Auto PSCT is 7 months. Maintenance therapy with bortezomib will be given for 2 years.
|- Main changes (audit trail)|
|- RECORD||20-apr-2009 - 23-sep-2009|