Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	Other	EBMT-EBMTLYM1 BNLI-EBMT-EBMTLYM1, EU-99050, NCT00005589

Objectives

1. Determine the effects of in vivo rituximab purging and maintenance on progression-free survival in patients with relapsed or resistant follicular non-Hodgkin's lymphoma undergoing high-dose chemotherapy.
2. Determine the effects of this regimen on response rate and overall survival in this patient population.
3. Determine the effects of in vivo purging with rituximab on molecular remission rates in the hematopoietic product and the patients.
4. Determine the safety of rituximab in the transplant setting.

Entry Criteria

Disease Characteristics:

• Relapsed or resistant follicular non-Hodgkin's lymphoma (NHL)
  • No evidence of transformation to high grade or diffuse large B-cell NHL



• CD20 positive with no evidence of transformation



• Achievement of complete remission (CR) or very good partial remission (VGPR) following reinduction chemotherapy with any standard regimen
  • Includes patients who fail to respond to first-line chemotherapy but who achieve CR or VGPR after proceeding directly to second-line chemotherapy



• Platelet count greater than 100,000/mm³ after induction chemotherapy and before randomization



• No CNS involvement

Prior/Concurrent Therapy:

Biologic therapy:

• More than 12 months since prior CD20 therapy, including rituximab
• No prior peripheral blood stem cell transplantation

Chemotherapy:

• See Disease Characteristics
• No more than 3 prior chemotherapy regimens for NHL

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to greater than 30% of bone marrow

Surgery:

• Not specified

Patient Characteristics:

Age:

• 18 and over

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin normal
• ALT no greater than 2 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
• Hepatitis B negative
• Hepatitis C negative

Renal:

• Creatinine no greater than 2 times ULN
• BUN no greater than 2 times ULN

Cardiovascular:

• No inadequate cardiac function

Pulmonary:

• No inadequate pulmonary function

Other:

• Not pregnant or nursing
• HIV negative
• No other uncontrolled serious medical conditions
• No other malignancy within the past 5 years except nonmelanoma skin tumors or carcinoma in situ of the cervix

Expected Enrollment

A total of 460 patients (115 per treatment arm) will be accrued for this study within 5 years.

Outcomes

Time to disease progression

Response rate and survival
Molecular remission rates
Safety

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to type of remission (complete vs good partial) and which remission (second vs third). Patients are randomized to one of four treatment arms.

All patients receive induction chemotherapy comprising cyclophosphamide IV over 3-4 hours on day 0 or a standard induction chemotherapy regimen. Filgrastim (G-CSF) is administered subcutaneously daily beginning on day 1.

Patients are then randomized to receive either in vivo rituximab purging or no purging following restaging after completion of induction. For those patients receiving purging (arms I and II), rituximab is administered IV once weekly for 4 weeks.

Peripheral blood stem cells (PBSC) are collected between days 8 and 12 post induction chemotherapy. Within 4 weeks of PBSC collection, patients receive carmustine IV over 2 hours on day -6, etoposide IV over 2 hours on days -5 to -2, cytarabine IV over 5 minutes twice daily on days -5 to -2, and melphalan IV over 10-15 minutes on day -1. (Alternatively, high dose cyclophosphamide and total body irradiation beginning 2-4 weeks after cyclophosphamide or standard induction chemotherapy priming is also allowed.) PBSC are reinfused on day 0.

Patients are further randomized to receive either rituximab maintenance or observation only. For those patients receiving maintenance (arms I and III), rituximab is administered IV once every 2 months for 4 doses beginning 30 days after PBSC reinfusion.

Patients are followed at 30 days, 3, 6, 9, and 12 months after PBSC transplant, every 6 months for 2 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

EBMT Solid Tumors Working Party

Ruth Pettengell, MD, Protocol chair		Ph: 44-208-725-5454 Email: r.pettengell@sgul.ac.uk

Lymphoma Trials Office

David C. Linch, Protocol chair		Ph: 44-171-380-9724

Registry Information
Official Title		Randomized Study of Rituximab (Mabthera) in Patients with Relapsed Follicular Lymphoma Prior to High-Dose Therapy as In Vivo Purging and to Maintain Remission Following High-Dose Therapy
Trial Start Date		1999-10-01
Registered in ClinicalTrials.gov		NCT00005589
Date Submitted to PDQ		2000-01-13
Information Last Verified		2007-03-27

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