Clinical trial NCT00514475: Zevalin-BEAM/BEAC With Autologous Stem Cell Support as Consolidation in First Line Treatment of Mantle Cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mantle Cell Lymphoma
Keywords: Mantle cell lymphoma
Zevalin
90Y-ibritumomab tiuxetan
Radioimmunotherapy
High-dose therapy
First line
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2007-08-10
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion criteria:

1. Age 18 - 65 years.
2. 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.
3. 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.
4. WHO performance status of 0 - 3.
5. Life expectancy of more than 3 months.
6. Written informed consent.

Exclusion Criteria:

1. Severe cardiac disease: cardiac function grade 3-4 (Appendix 1).
2. Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment.
3. Pregnancy/lactation
4. 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.
5. Known HIV positivity
6. Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma.
7. Known seropositivity for HCV, HbsAg or other active infection uncontrolled by treatment.
8. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.

Primary outcomes:
measure: Time to treatment failure (TTF) for PR/CRu patients receiving Zevalin-BEAM/BEAC
timeFrame: 3 years
Secondary outcomes:
measure: Safety
timeFrame: Whole study
measure: TTF for CR patients receiving BEAM/BEAC
timeFrame: 3 year
measure: Overall survival
timeFrame: 5 year
measure: Time to progression
timeFrame: 3 year
measure: Response rates
timeFrame: 6 months
measure: Value of PET
timeFrame: 6 months
measure: Molecular response rates
timeFrame: 6 months
measure: Molecular response and progression-free survival after Rituximab for molecular relapse
timeFrame: 5 years
measure: Microarray gene expression analysis
timeFrame: 5 years
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Arne Kolstad
Study officials:
affiliation: Nordic Lymphoma Group
name: Arne Kolstad, MD
role: STUDY_CHAIR
affiliation: Nordic Lymphoma Group
name: Christian Geisler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nordic Lymphoma Group
name: Erkki Elonen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nordic Lymphoma Group
name: Anna Laurell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kolstad A, Laurell A, Jerkeman M, Gronbaek K, Elonen E, Raty R, Pedersen LB, Loft A, Bogsrud TV, Kimby E, Hansen PB, Fagerli UM, Nilsson-Ehle H, Lauritzsen GF, Lehmann AK, Sundstrom C, Karjalainen-Lindsberg ML, Ralfkiaer E, Ehinger M, Delabie J, Bentzen H, Schildt J, Kostova-Aherdan K, Frederiksen H, Brown Pde N, Geisler CH; Nordic Lymphoma Group. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma. Blood. 2014 May 8;123(19):2953-9. doi: 10.1182/blood-2013-12-541953. Epub 2014 Mar 20.