Zevalin-BEAM/BEAC With Autologous Stem Cell Support as Consolidation in First Line Treatment of Mantle Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of the study is to determine if outcome for patients with mantle cell lymphoma is improved by adding radioimmunotherapy to high-dose regimen before auto-transplant in patients who are not in CR after induction therapy.

Detailed Description
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Mantle cell lymphoma is considered to have the worst outcome of all non-Hodgkins lymphomas. Since 1997, the Nordic Lymphoma Group has conducted phase II studies in order to improve the results for this lymphoma subtype. The first study included high-dose therapy with autologous stem cell support in the first line of treatment. The results showed the importance of a high quality response to pre-transplant induction treatment, and that CHOP-based regimen alone did not achieve this. Thus, the second trial was designed to improve remissions by including Rituximab and high-dose Ara-C. Results now show that a high rate of molecular remission in the bone marrow was achieved, and the 3-year FFS was improved in comparison to the first study (80% vs 24%). Furthermore, patient who had a molecular relapse (t(11;14) or IgV-gene) were treated with 4 doses of Rituximab and many converted back to be PCR negative. The present and thus third phase II study aims to improve the high-dose regimen by adding Zevalin radioimmunotherapy in patients who are not in CR prior to transplant. Data from the last trial show that patients not in CR at this point have a worse outcome (3 year FFS of 63%, vs 85% for CR patients). Monitoring for molecular relapse in the bone marrow will be done, and patients who become PCR positive will be treated with Rituximab in order to evaluate the value of this strategy.

Official Title
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High-dose Therapy With Autologous Stem Cell Support in First Line Treatment of Mantle Cell Lymphoma- 90Y-Ibritumomab Tiuxetan in Combination With BEAM or BEAC to Improve Outcome for Patients Not in CR After Induction Treatment

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: 90Y-ibritumomab tiuxetan (Zevalin)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age 18 - 65 years. Histologically confirmed (according to the WHO classification) mantle cell lymphoma stage II-IV at time point of diagnosis. The diagnosis has to be confirmed by phenotypic expression of CD5, CD20 and cyclin-D1 and most cases will have t(11;14) translocation. No previous treatment for lymphoma except radiotherapy or one cycle of any regimen and except patients treated in the previous phase II study who can be transferred to NLG-MCL-III before evaluation at week 15. WHO performance status of 0 - 3. Life expectancy of more than 3 months. Written informed consent. Exclusion Criteria: Severe cardiac disease: cardiac function grade 3-4 (Appendix 1). Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment. Pregnancy/lactation Men or woman of reproductive potential not agreeing to use acceptable method of birth control during treatment and for six moths after completion of treatment. Known HIV positivity Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma. Known seropositivity for HCV, HbsAg or other active infection uncontrolled by treatment. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 90Y-ibritumomab tiuxetan (Zevalin)|90Y-ibritumomab tiuxetan (Zevalin) at 0.4 mCi/kg is administered one week prior to start high-dose chemotherapy (BEAM/BEAC) in patients who have not achieved CR after induction therapy. Predosing with rituximab 250 mg/m2 one weeks prior to radioimmunotherapy and the same day.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment failure (TTF) for PR/CRu patients receiving Zevalin-BEAM/BEAC |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | Whole study | 
| TTF for CR patients receiving BEAM/BEAC |  | 3 year | 
| Overall survival |  | 5 year | 
| Time to progression |  | 3 year | 
| Response rates |  | 6 months | 
| Value of PET |  | 6 months | 
| Molecular response rates |  | 6 months | 
| Molecular response and progression-free survival after Rituximab for molecular relapse |  | 5 years | 
| Microarray gene expression analysis |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mantle cell lymphoma, Zevalin, 90Y-ibritumomab tiuxetan, Radioimmunotherapy, High-dose therapy, First line