Zevalin With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Non Hodgkin Lymphoma

Non-Hodgkins Lymphoma Clinical Trial

Official title:

Phase I-II Non-Randomized Study of Yttrium 90 Ibritumomab Tiuxetan (Zevalin) With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Relapsed, Refractory, or Transformed Indolent Non Hodgkin Lymphoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00807196
• Other study ID #: ZEV0701
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: December 10, 2008
• Last updated: December 10, 2008
• Start date: September 2008
• Est. completion date: December 2012

Study information

• Verified date: December 2008
• Source: Maisonneuve-Rosemont Hospital
• Contact: Thomas Kiss, MD
• Phone: 514-252-3404
• Email: thomas.kiss[@]umomtreal.ca
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the ability to combine a radioactive medication directly targeted against lymphoma cells with the immune effects of an allogeneic blood stem cell transplant.

Description:

Despite initial high response rates of low grade Non Hodgkin lymphoma, progressive or refractory disease currently remains incurable. Being a radiosensitive tumor, we hypothesize that combining different modalities of treatment including targeted radioimmunotherapy (RIT), and a graft versus lymphoma effect related to an allogeneic non myeloablative stem cell transplant may increase response and survival rates in a safe manner in patients with persistent disease following initial treatment. In this study patients who are not eligible for a standard stem cell transplant approach because of relapsed or refractory disease and who have a related sibling donor are treated with RIT followed by an allogeneic non myeloablative blood stem cell transplant

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Patients must have/be

1. Age 18 to 65 years. Patients between age 66 and 69 may be enrolled if judged to be in excellent physical condition as per treating physician and study investigator and based on institutional practice.

2. Diagnosis of Non-Hodgkin lymphoma, follicular, marginal zone, small lymphocytic lymphoma, mantle cell lymphoma or transformed from an indolent NHL to aggressive histology disease lymphoma as defined by the World Health Organization.

3. Disease relapsed after, refractory or failing to achieve a PR after two or more cycles of intensive salvage chemotherapy (R-ESHAP or other) or disease relapsed after autologous stem cell transplantation. Poor partial response is defined as less than 50% reduction of tumor size. Salvage chemotherapy has to be administered after either 1st, 2nd or 3rd relapse

4. Disease expressing the CD 20 antigen

5. ECOG performance status 0-2

6. Judged to be able to tolerate NST and Zevalin treatment based on institutional criteria.

7. Signed written informed consent

8. At least one fully HLA matched sibling without evident contraindications to the donation procedures and willing to sign consent for donation

Exclusion Criteria:

Patients must not have/be

1. Abnormal renal function (creatinine > 1.5 x upper limit of normal (ULN)

2. Abnormal hepatic function (bilirubin > 2 x ULN, ALT/AST>2x ULN)

3. Cardiac ejection fraction <40% and/or other significant cardiac compromise

4. Severe defects in pulmonary function tests or receiving continuous oxygen

5. Severe concurrent illness, such as symptomatic congestive heart failure, severe arrhythmias, uncontrolled hypertension, diabetes, severe neurologic or psychiatric disorder or known HIV positive

6. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) that may impact on patients life expectancy or any cancer curatively treated < 3 years prior to study entry.

7. History of prior allogeneic bone marrow transplant

8. Evidence of active hepatitis B or C infection or positivity for hepatitis-B surface antigen

9. Known type 1 hypersensitivity or anaphylactic proteins to any component of the Zevalin therapy or a history or presence of human anti-mouse antibodies (HAMA)

10. A female patient who is pregnant or breast feeding and an adult of reproductive potential who is not employing an effective method of birth control during the study.

11. CNS lymphoma

12. Ongoing confirmed or suspected significant infection

13. Prior treatment with radioimmunotherapy

14. Other condition preventing participation in standard NST

15. No fully matched sibling donor

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkins Lymphoma

Intervention

Drug:
• Rituximab
250mg/m2 day -21 and day -14 of preparative regimen
• 90Y ibritumomab tiuxetan (Zevalin)
0.4 mCi/kg IV on day -14 of preparative regimen
• Cyclophosphamide
300mg/m2 IV daily for 5 days day -8 to day -4 of preparative regimen
• Fludarabine
30mg/m2 IV daily for 5 days day -8 to day -4 of preparative regimen

Other:
• Non myeloablative allogeneic stem cell transplantation
Blood stem cell infusion on day 0

Locations

Country	Name	City	State
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Maisonneuve-Rosemont Hospital	Bayer

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Engraftment, chimerism, transplant related toxicity, acute and chronic GVHD		one year	Yes
Secondary	Overall response rate, overall and disease free survival		360 days	Yes