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

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514475
• Other study ID #: 2005-002003-17
• Status: Completed
• Phase: Phase 2
• First received: August 9, 2007
• Last updated: May 3, 2012
• Start date: November 2005
• Est. completion date: June 2009

Study information

• Verified date: May 2008
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00505674

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Norway	Arne Kolstad	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to treatment failure (TTF) for PR/CRu patients receiving Zevalin-BEAM/BEAC		3 years	No
Secondary	Safety		Whole study	Yes
Secondary	TTF for CR patients receiving BEAM/BEAC		3 year	No
Secondary	Overall survival		5 year	No
Secondary	Time to progression		3 year	No
Secondary	Response rates		6 months	No
Secondary	Value of PET		6 months	No
Secondary	Molecular response rates		6 months	No
Secondary	Molecular response and progression-free survival after Rituximab for molecular relapse		5 years	No
Secondary	Microarray gene expression analysis		5 years	No

External Links

•   Web site for the Nordic Lymphoma Group