Ibritumomab Tiuxetan for Treatment of Non-Follicular CD20+ Indolent Lymphomas

Lymphoma Clinical Trial

Official title:

Multicenter Phase II Study for Zevalin® in Patients With Relapsed/Refractory Indolent Lymphomas: Extranodal Marginal Lymphoma of MALT Type, Nodal Marginal Zone B-Cell Lymphoma, and Splenic Marginal B-Cell Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00493454
• Other study ID #: 2005-0571
• Status: Terminated
• Phase: Phase 2
• First received: June 27, 2007
• Last updated: May 30, 2013
• Start date: April 2006
• Est. completion date: March 2011

Study information

• Verified date: May 2013
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Primary Objective:

• Overall Response Rate (ORR).

Secondary Objectives:

• The Duration of Response (DR) and Time to Treatment Progression (TTP) in all patients and in the responders.

• Complete Responses (CR)/Complete Responses unconfirmed (CRu), and Partial Responses (PR).

• Time to next anticancer therapy (TTNT).

Description:

^90 Y Ibritumomab tiuxetan and rituximab are both designed to attach to lymphoma cells, causing them to die.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a physical exam. Your blood (about 2 to 3 teaspoons) and urine will be collected for routine tests. You will have a chest x-ray and computerized tomography (CT) scans of the neck, chest, abdomen, and pelvis. You will have a bone marrow aspirate and biopsy performed. To collect a bone marrow aspirate and biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood pregnancy test.

The study doctors will first make sure that your disease has not spread too much and is not too severe to require immediate treatment with chemotherapy before you can begin treatment on this study. If you are found to be eligible to take part in this study, you will be given Benadryl (diphenhydramine) by vein, and you will be given Tylenol (acetaminophen) by mouth before each dose of rituximab. This is done to help decrease the risk of developing side effects of rituximab. You will then receive 1 dose of rituximab by vein over 6 to 8 hours on Day 1 of treatment. After treatment with rituximab, you will then be given a radioactive antibody, ^111 In Ibritumomab tiuxetan (this is a radioactive agent that binds to rituximab to help with imaging exams), by vein over about 10 minutes. This is so researchers can use a special camera to see where the drug is in your body.

You will have imaging performed (with the special camera) on Day 1 and on either Day 2 or Day 3. On Day 8, you will receive a second dose of rituximab. This will then be followed by a dose ^90 Y Ibritumomab tiuxetan of given by vein over 10 minutes. This completes the treatment.

If you experience intolerable side effects while on this study, you may be removed from this study. The study doctor will then offer other treatment options to you.

For your follow-up, you will have blood (about 2 tablespoons) drawn once a week for the first 3 months, then every 3 months for 1 year, and then every 4 months for the second year. At these visits, you may also have CT scans, x-rays, and bone marrow biopsies and aspirates performed, if needed.

This is an investigational study. ^90 Y Ibritumomab tiuxetan and rituximab have been approved by the FDA for the treatment of indolent B-cell lymphoma. Up to 35 patients will take part in this multicenter study. Up to 15 will be enrolled at M. D. Anderson.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. No anti-cancer therapy for three weeks (six weeks if Rituximab, nitrosourea or Mitomycin C) prior to study initiation, and fully recovered from acute toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy.

2. Previously treated patients with a histology of refractory/relapsed indolent lymphomas including: (a) Extranodal marginal lymphoma of MALT type; (b) Nodal Marginal zone B-cell lymphoma (+/- monocytoid cells); (c) Splenic marginal B-cell lymphoma (+/- villous lymphocytes).

3. Signed informed consent

4. Age >/= 18 years

5. Expected survival >/= 3 months

6. Pre-study Zubrod performance status of 0, 1, or 2

7. Acceptable hematologic status within two weeks prior to patient registration, including: (a) Absolute neutrophil count ([segmented neutrophils + bands] * total white blood count (WBC)) >/= 1,500/mm^3; (b) Platelet counts >/= 100,000/mm^3.

8. Female patients who are not pregnant or lactating

9. Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician)

10. Patients previously on Phase II drugs if no long-term toxicity is expected, and the patient has been off the drug for eight or more weeks with no significant post treatment toxicities observed

11. Patients determined to have < 25% bone marrow involvement with lymphoma within six weeks of registration (define measurement of a bone marrow aspirate or biopsy) (This criteria must be strictly met for adequate patient safety.)

12. Patient should have at least one lesion measuring >/= 2 cm in a single dimension.

Exclusion Criteria:

1. Prior myeloablative therapies with autologous bone marrow transplantation (ABMT) or peripheral blood stem cell (PBSC) rescue.

2. Platelet count< 100,000 cells/mm^3.

3. Presence of hypocellular bone marrow.

4. Patients with history of failed stem cell collection.

5. Prior radioimmunotherapy

6. Presence of Central Nervous System (CNS) lymphoma

7. Patients with HIV.

8. Patients with pleural effusion

9. Patients with abnormal liver function: total bilirubin > 2.0 mg/dL

10. Patients with abnormal renal function: serum creatinine > 2.0 mg/dL

11. Patients who have received prior external beam radiation therapy to > 25% of active bone marrow (involved field or regional)

12. Patients who have received short-acting growth factor support (Leukine, Neupogen, Procrit) within 2 weeks prior to treatment or long-acting growth-factor support (Aranesp), Neulasta) within 4 weeks prior to treatment.

13. Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives

14. Major surgery, other than diagnostic surgery, within four weeks

15. Evidence of transformation in the latest biopsy

Study Design

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• Zevalin
.3 mCi IV Over 10 Minutes x 1 Day
• Rituximab
250 mg/m^2 IV Over 6 to 8 Hours
• ^111 In Ibritumomab Tiuxetan
1.6 mg IV Over 10 Minutes x 1 Day

Locations

Country	Name	City	State
United States	UT MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Objective response rate (ORR) = number of participants out of all participating with Complete Response (CR) + Partial Response (PR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Partial response (PR) must have = 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. Response assessed by magnetic resonance imaging (MRI) or computed tomography (CT) scans, every 3 months for the first year and every 6 months up to 3 years following.	Evaluation 4 weeks after administration of Zevalin up to 3 years	No

External Links

•   The University of Texas M.D.Anderson Cancer Center Official Web Site