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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-Hodgkins Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: 90Y ibritumomab tiuxetan (Zevalin); Drug: Cyclophosphamide; Drug: Fludarabine; Other: Non myeloablative allogeneic stem cell transplantation

Detailed 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

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2V 1W7
      • Recruiting
      • Hopital Maisonneuve-Rosemont
      • Contact: Thomas Kiss, MD; Phone Number: (514)252-3404; Email: thomas.kiss@umontreal.ca
      • Contact: Dominique Beaupré, BSc nursing; Phone Number: 5605 (514)252-3400; Email: dbeaupré.hmr@ssss.gouv.qc.ca
      • Principal Investigator: Thomas Kiss, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: T

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Engraftment, chimerism, transplant related toxicity, acute and chronic GVHD	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall response rate, overall and disease free survival	360 days

Collaborators and Investigators

• Sponsor: Maisonneuve-Rosemont Hospital
• Collaborators: Bayer
• Investigators: Principal Investigator: Thomas Kiss, MD, Maisonneuve-Rosemont Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ANTICIPATED): December 1, 2011
• Study Completion (ANTICIPATED): December 1, 2012

Study Registration Dates

• First Submitted: December 10, 2008
• First Submitted That Met QC Criteria: December 10, 2008
• First Posted (ESTIMATE): December 11, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): December 11, 2008
• Last Update Submitted That Met QC Criteria: December 10, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Allogeneic Stem Cell Transplantation; Non-Hodgkins Lymphoma; Zevalin
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab; Fludarabine
• Other Study ID Numbers: ZEV0701