Radiolabeled Monoclonal Antibody Therapy and High-Dose Chemotherapy Followed By Autologous Peripheral Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Phase 1

Completed

• Conditions: Lymphoma
• Interventions: Biological: filgrastim; Biological: rituximab; Drug: Carmustine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation; Radiation: yttrium Y 90 ibritumomab tiuxetan

• Registration Number: NCT00058292
• Lead Sponsor: Northwestern University

Brief Summary

RATIONALE: Radiolabeled monoclonal antibodies such as yttrium Y90 ibritumomab tiuxetan can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining yttrium Y90 ibritumomab tiuxetan and chemotherapy with autologous stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase I trial is studying how well giving yttrium Y90 ibritumomab tiuxetan with high-dose chemotherapy followed by autologous stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

* Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan, in terms of absorbed radiation to critical organs, when administered with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

* Determine whether the residual radioactivity detected at the time of stem cell reinfusion affects the reinfused cells and delays engraftment in patients treated with this regimen.

* Determine the duration of response and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).

* Radioimmunotherapy: Patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -22. Patients then receive rituximab IV and IDEC-Y2B8 IV over 10 minutes on day -14.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

* High-dose conditioning regimen: Patients receive BEAM chemotherapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 2 hours twice daily and cytarabine IV over 1 hour twice daily on days -5 to -2, and melphalan IV over 1 hour on day -1.

* Autologous stem cell transplantation: Autologous peripheral blood stem cells are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily beginning on day 0 and continuing until blood counts recover.

Patients are followed at 30 days, 3 and 6 months, and then annually for 5 years.

PROJECTED ACCRUAL: A maximum of 42 patients will be accrued for this study.

Study Timeline

• Study Start: 2000-04
• Study First Submitted: 2003-04-07
• Study First Submitted QC: 2003-04-08
• Study First Posted: 2003-04-09
• Primary Completion: 2006-06
• Study Completion: 2009-03
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-31
• Last Update Posted: 2012-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	filgrastim	-
Treatment Arm	rituximab	-
Treatment Arm	Carmustine	-
Treatment Arm	melphalan	-
Treatment Arm	peripheral blood stem cell transplantation	-
Treatment Arm	yttrium Y 90 ibritumomab tiuxetan	-
Treatment Arm	cytarabine	-
Treatment Arm	etoposide	-

Primary Outcome Measures

Name	Time	Method
Determine the maximum tolerated dose of absorbed radiation to critical organs delivered with this combination of study treatments	From first study treatment until 30 days after last study treatment.	Dose limiting toxicities observed during and up to 30 days after the last study treatment resulting in the determination of the maximum tolerated dose of absorbed radiation to critical organs delivered by Y2B8 in combination with high-dose BEAM chemotherapy with autologous mobilized peripheral blood progenitor cell transplant

Trial Locations

Locations (3)

Robert H. Lurie Comprehensive Cancer Center at Northwestern University; 🇺🇸 Chicago, Illinois, United States

Hematology-Oncology Associates of Illinois; 🇺🇸 Chicago, Illinois, United States

Mayo Clinic Cancer Center; 🇺🇸 Rochester, Minnesota, United States