Know Cancer

forgot password

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

Phase 3
18 Years
Open (Enrolling)

Thank you

Trial Information

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


- 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.

- Determine the effects of this regimen on response rate and overall survival in this
patient population.

- Determine the effects of in vivo purging with rituximab on molecular remission rates in
the hematopoietic product and the patients.

- Determine the safety of rituximab in the transplant setting.

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.

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

Inclusion Criteria


- 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/mm^3 after induction chemotherapy and before

- No CNS involvement



- 18 and over

Performance status:

- WHO 0-1

Life expectancy:

- Not specified


- See Disease Characteristics


- 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


- Creatinine no greater than 2 times ULN

- BUN no greater than 2 times ULN


- No inadequate cardiac function


- No inadequate pulmonary function


- 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


Biologic therapy:

- More than 12 months since prior CD20 therapy, including rituximab

- No prior peripheral blood stem cell transplantation


- See Disease Characteristics

- No more than 3 prior chemotherapy regimens for NHL

Endocrine therapy:

- Not specified


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


- Not specified

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to disease progression

Safety Issue:


Principal Investigator

Ruth Pettengell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

St George's, University of London


United States: Federal Government

Study ID:




Start Date:

October 1999

Completion Date:

Related Keywords:

  • Lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin