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

Primary Purpose

Mantle Cell Lymphoma

Status

Completed

Phase

Phase 2

Locations

Norway

Study Type

Interventional

Intervention

90Y-ibritumomab tiuxetan (Zevalin)

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring Mantle cell lymphoma, Zevalin, 90Y-ibritumomab tiuxetan, Radioimmunotherapy, High-dose therapy, First line

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arne Kolstad

Outcomes

Primary Outcome Measures

Time to treatment failure (TTF) for PR/CRu patients receiving Zevalin-BEAM/BEAC

Secondary Outcome Measures

Safety

TTF for CR patients receiving BEAM/BEAC

Overall survival

Time to progression

Response rates

Value of PET

Molecular response rates

Molecular response and progression-free survival after Rituximab for molecular relapse

Microarray gene expression analysis

Full Information

NCT ID

NCT00514475

First Posted

August 9, 2007

Last Updated

May 3, 2012

Sponsor

Oslo University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00514475

Brief Title

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

2. Study Status

Record Verification Date

May 2008

Overall Recruitment Status

Completed

Study Start Date

November 2005 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Oslo University Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Mantle Cell Lymphoma

Keywords

Mantle cell lymphoma, Zevalin, 90Y-ibritumomab tiuxetan, Radioimmunotherapy, High-dose therapy, First line

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

160 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

90Y-ibritumomab tiuxetan (Zevalin)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time to treatment failure (TTF) for PR/CRu patients receiving Zevalin-BEAM/BEAC

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Safety

Time Frame

Whole study

Title

TTF for CR patients receiving BEAM/BEAC

Time Frame

3 year

Title

Overall survival

Time Frame

5 year

Title

Time to progression

Time Frame

3 year

Title

Response rates

Time Frame

6 months

Title

Value of PET

Time Frame

6 months

Title

Molecular response rates

Time Frame

6 months

Title

Molecular response and progression-free survival after Rituximab for molecular relapse

Time Frame

5 years

Title

Microarray gene expression analysis

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arne Kolstad, MD

Organizational Affiliation

Nordic Lymphoma Group

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Christian Geisler, MD

Organizational Affiliation

Nordic Lymphoma Group

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Erkki Elonen, MD

Organizational Affiliation

Nordic Lymphoma Group

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Anna Laurell, MD

Organizational Affiliation

Nordic Lymphoma Group

Official's Role

Principal Investigator

Facility Information:

Facility Name

Arne Kolstad

City

Oslo

ZIP/Postal Code

0310

Country

Norway

12. IPD Sharing Statement

Citations:

PubMed Identifier

24652994

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.

Results Reference

derived

Links:

URL

http://www.nordic-lymphoma.org

Description

Web site for the Nordic Lymphoma Group

Learn more about this trial

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

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