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

This study has been completed.
Sponsor:
Collaborator:
Lymphoma Trials Office
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005589
First received: May 2, 2000
Last updated: September 16, 2013
Last verified: March 2007
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combination chemotherapy plus peripheral stem cell transplantation is more effective with or without rituximab for non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy and peripheral stem cell transplantation together with rituximab to see how well it works compared to combination chemotherapy and peripheral stem cell transplantation alone in treating patients with relapsed non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carmustine
Drug: cyclophosphamide
Drug: cytarabine
Drug: etoposide
Drug: melphalan
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to disease progression [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate and survival [ Designated as safety issue: No ]
  • Molecular remission rates [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]

Estimated Enrollment: 460
Study Start Date: October 1999
Study Completion Date: April 2013
Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/mm^3 after induction chemotherapy and before randomization
  • No CNS involvement

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005589

  Show 131 Study Locations
Sponsors and Collaborators
EBMT Solid Tumors Working Party
Lymphoma Trials Office
Investigators
Study Chair: Ruth Pettengell, MD St George's, University of London
Study Chair: David C. Linch Middlesex Hospital
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00005589     History of Changes
Other Study ID Numbers: CDR0000067665, EBMT-EBMTLYM1, BNLI-EBMT-EBMTLYM1, EU-99050
Study First Received: May 2, 2000
Last Updated: September 16, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Cyclophosphamide
Melphalan
Rituximab
Cytarabine
Etoposide
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on August 18, 2014