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

Sponsor:	Oslo University Hospital
Information provided by (Responsible Party):	Oslo University Hospital
ClinicalTrials.gov Identifier:	NCT00514475

Purpose

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.

Condition	Intervention	Phase
Mantle Cell Lymphoma	Drug: 90Y-ibritumomab tiuxetan (Zevalin)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Ibritumomab tiuxetan

U.S. FDA Resources

Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:

Time to treatment failure (TTF) for PR/CRu patients receiving Zevalin-BEAM/BEAC [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety [ Time Frame: Whole study ] [ Designated as safety issue: Yes ]
TTF for CR patients receiving BEAM/BEAC [ Time Frame: 3 year ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: 5 year ] [ Designated as safety issue: No ]
Time to progression [ Time Frame: 3 year ] [ Designated as safety issue: No ]
Response rates [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Value of PET [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Molecular response rates [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Molecular response and progression-free survival after Rituximab for molecular relapse [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Microarray gene expression analysis [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment:	160
Study Start Date:	November 2005
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514475

Locations

Norway
Arne Kolstad
Oslo, Norway, 0310

Sponsors and Collaborators

Oslo University Hospital

Investigators

Study Chair:	Arne Kolstad, MD	Nordic Lymphoma Group
Principal Investigator:	Christian Geisler, MD	Nordic Lymphoma Group
Principal Investigator:	Erkki Elonen, MD	Nordic Lymphoma Group
Principal Investigator:	Anna Laurell, MD	Nordic Lymphoma Group

More Information

Additional Information:

Web site for the Nordic Lymphoma Group This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Oslo University Hospital, MD PhD
ClinicalTrials.gov Identifier:	NCT00514475 History of Changes
Obsolete Identifiers:	NCT00505674
Other Study ID Numbers:	2005-002003-17
Study First Received:	August 9, 2007
Last Updated:	May 3, 2012
Health Authority:	Norway: Norwegian Medicines Agency

Keywords provided by Oslo University Hospital:

Mantle cell lymphoma
Zevalin
90Y-ibritumomab tiuxetan

Radioimmunotherapy
High-dose therapy
First line

Additional relevant MeSH terms:

Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 31, 2012