Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin’s Lymphoma

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. 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 whether chemotherapy is more effective with or without rituximab for relapsed non-Hodgkin’s lymphoma.

Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating patients who have relapsed non-Hodgkin’s lymphoma.

Official Title

Phase III Randomized Study of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone With or Without Rituximab in Patients With Relapsed Follicular Non-Hodgkin’s Lymphoma

Conditions

Non-Hodgkin’s Lymphomas’:- grade 1 follicular lymphoma- grade 2 follicular lymphoma- grade 3 follicular lymphoma

Study Type

Interventional

Study Design

Treatment

Further Details

OBJECTIVES:- Compare the response rate and quality of remission in patients with relapsed follicular non-Hodgkin’s lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab. – Compare the event-free survival and overall survival of patients treated with these regimens. – Determine the effect of rituximab as maintenance therapy on progression-free survival of these patients. OUTLINE: This is a randomized, multicenter study.Induction:- Patients are randomized to one of two treatment arms. Patients are stratified according to participating center, prior treatment with purine analogues, age, number of prior induction treatments and best response obtained (complete vs partial remission vs no change/progressive disease), time since diagnosis (less than 2 years vs more than 2 years), and bulky disease (less than 10 cm vs greater than 10 cm). – Arm I: Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5 (CHOP chemotherapy). Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. -Arm II: Patients receive CHOP chemotherapy as in arm I. Rituximab IV is administered 1 hour after prednisone and before the IV drugs. Maintenance:- Patients who achieve partial or complete remission are then randomized to one of two treatment arms. Patients are stratified according to rituximab administration during induction (yes vs no), quality of the response (complete vs partial remission vs no change/progressive disease), and participating center. – Arm I: Patients receive no further therapy. – Arm II: Beginning 8 weeks after the last CHOP course, patients receive rituximab IV once every 3 months for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 4 months thereafter.

Study Start

Eligibility & Criteria

DISEASE CHARACTERISTICS:- Histologically or cytologically proven stage III or IV follicular non-Hodgkin’s lymphoma (NHL) – Relapsed after or no response (no change/progressive disease) to no more than 2 adequate non-anthracycline-containing systemic chemotherapy regimens – At least 2 months of single-agent therapy (e.g., chlorambucil) AND/OR – At least 2 consecutive courses of polychemotherapy (e.g., cyclophosphamide, vincristine, and prednisone) or purine analogues – Complete or partial remission or no change for at least 4 weeks after completion of prior therapy OR progression during one of a maximum of 2 prior therapy regimens – CD20 positive – At least 1 bidimensionally measurable mass – No greater than 10,000,000/mL circulating tumor cells – IgG levels at least 3 g/L – No low-grade NHL transformed into intermediate- or high-grade NHL – No symptomatic CNS lymphoma – No bone marrow involvement only NOTE: A new classification scheme for adult non-Hodgkin’s lymphoma has been adopted by PDQ. The terminology of “indolent” or “aggressive” lymphoma will replace the former terminology of “low”, “intermediate”, or “high” grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age:- 18 and over Male or FemalePerformance status:- WHO 0-2 – Bilirubin less than 2.5 times upper limit of normal (ULN) – Alkaline phosphatase less than 2.5 times ULN Renal:- Creatinine less than 2.5 times ULN – BUN less than 2.5 times ULN Cardiovascular:- No severe cardiac disease (i.e., severe heart failure requiring symptomatic treatment) Pulmonary:- No severe pulmonary disease Other:- No severe neurologic or psychiatric disease – No severe metabolic disease – Not pregnant – Fertile patients must use effective contraception – No prior malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other cancer curatively treated with surgical therapy – HIV negative – No uncontrolled asthma or allergy requiring steroids – No known hypersensitivity or prior anaphylactic reaction to murine proteins or any component of study drug PRIOR CONCURRENT THERAPY: Biologic therapy:- No prior rituximab – No prior allogeneic or autologous peripheral blood stem cell transplantation – Concurrent filgrastim (G-CSF) for stem cell mobilization allowed Chemotherapy:- See Disease Characteristics – No prior anthracyclines or mitoxantrone – No concurrent chemotherapy for stem cell mobilization

Total Enrolment

A total of 752 patients will be accrued for this study within 6 years.

Contact Details

[1] Australasian Leukemia and Lymphoma GroupAustralia, Australian Capital Territory Canberra Hospital, Garran, Australian Capital Territory, 2605, Australia; Recruiting Ian Prosser, MD 61-2-6244-2830 ian.prosser@act.gov.au Australia, New South Wales Albury Base Hospital, Albury, New South Wales, 2640, Australia; Recruiting Contact Person 45-65-41-2921 Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia; Recruiting Stephen P. Mulligan, MD, PhD (61-2)9736-6648 Institute of Oncology at Prince of Wales Hospital, Randwick, New South Wales, 2031, Australia; Recruiting Contact Person 61-29-326-1798 Liverpool Hospital, Liverpool, New South Wales, 2170, Australia; Recruiting Contact Person 61-2-9828-4887 Newcastle Mater Misericordiae Hospital, Waratah, New South Wales, 2298, Australia; Recruiting Contact Person 61-2-4985-0113 Royal North Shore Hospital, St. Leonards, New South Wales, 2065, Australia; Recruiting Contact Person 61-2-438-7111 St. George Hospital, Sydney, New South Wales, 2217, Australia; Recruiting Tim Brighton, MD 61-2-9350-1111 St. Vincent’s Hospital, Sydney, New South Wales, 2010, Australia; Recruiting David Ma, MD 61-283-822-378 Sydney Cancer Centre at Royal Prince Alfred Hospital, Sydney, New South Wales, 2050, Australia; Recruiting Contact Person 61-2-516-8537 Wesley Medical Centre, Milton, New South Wales, 4064, Australia; Recruiting John Bashford, MD 61-7-3232-7000 Westmead Breast Centre at NSW Breast Cancer Institute, Westmead, New South Wales, 2145, Australia; Recruiting Mark Hertzberg, MD, PhD 61-2-9845-6728 markh@westgate.wh.usyd.edu.au Westmead Hospital, Westmead, New South Wales, 2145, Australia; Recruiting Contact Person 61-2-9891-6951 Wollongong Hospital, Wollongong, New South Wales, 2500, Australia; Recruiting Pauline Warburton, MD ISD 61-2-4222-5472 warburtonp@iahs.nsw.gov.au Australia, Queensland Greenslopes Private Hospital, Greenslopes, Queensland, 4120, Australia; Recruiting Contact Person 61-7-3394-7111 Mater Private Clinic, South Brisbane, Queensland, 4101, Australia; Recruiting Contact Person 61-73-7840-8111 Princess Alexandra Hospital, Brisbane, Queensland, 4102, Australia; Recruiting Contact Person 61-73-240-2111 Royal Brisbane and Women’s Hospital, Brisbane, Queensland, 4029, Australia; Recruiting Contact Person 61-73-253-8111 Townsville General Hospital, Townsville, Queensland, 4810, Australia; Recruiting Contact Person 617-4796-1634 Australia, South Australia Ashford Cancer Centre, Ashford, South Australia, 5035, Australia; Recruiting Francis Parnis, MD 61-8-351-0211 adeleridecancercentre@gigpond.com Flinder Medical Centres, Bedford Park, South Australia, 5042, Australia; Recruiting Bogda Koczwara, MD 61-8-204-8997 Queen Elizabeth Hospital, Woodville, South Australia, 5011, Australia; Recruiting Contact Person 61-8-243-6645 Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia; Recruiting Contact Person 61-8-8222-4000 Australia, Tasmania Royal Hobart Hospital, Hobart, Tasmania, 7000, Australia; Recruiting Contact Person 38 8308 Australia, Victoria Alfred Hospital, Melbourne, Victoria, 3181, Australia; Recruiting Contact Person 61-3-9276-2000 Austin Hospital, Heidelberg, Victoria, 3084, Australia; Recruiting Carole Smith, MD 61-3-9496-5093 Box Hill Hospital, Box Hill, Victoria, 3128, Australia; Recruiting Joe McKendrick, MD 039-895-3585 joe.mckendrick@boxhill.org.au Frankston Hospital, Frankston, Victoria, 3199, Australia; Recruiting Contact Person 61-3-9784-7777 Garden Consulting Rooms, Mornington, Victoria, 3931, Australia; Recruiting Vinod Ganju, MD 61-3-5976-0812 Geelong Hospital, Geelong, Victoria, 3200, Australia; Recruiting Contact Person 61-52-267-855 John Fawkner Hospital, Coburg, Victoria, 3058, Australia; Recruiting Walter Cosolo, MD 61-938-3-1811 Monash Medical Center, East Bentleigh, Victoria, 3165, Australia; Recruiting Contact Person 61-3-9550-1111 Peter MacCallum Cancer Centre, East Melbourne, Victoria, 8006, Australia; Recruiting Contact Person 61-3-9656-1111 Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia; Recruiting Contact Person 61-30-342-7000 St. John of God Hospital, Ballarat, Victoria, 3350, Australia; Recruiting Contact Person 61-53-316-677 St. Vincent’s Hospital, Fitzroy, Victoria, 3065, Australia; Recruiting Contact Person 613-288-2211 Australia, Western Australia Fremantle Hospital, Fremantle, Western Australia, 6160, Australia; Recruiting Michael Leahy, MBChB, FRACP, FRCP, FRC PATH 61-8-9431-2886 Mount Medical Centre, Perth, Western Australia, 6000, Australia; Recruiting Guy A. Van Hazel, MD 61-8-9481-3072 Royal Perth Hospital, Perth, Western Australia, 6000, Australia; Recruiting Contact Person 61-9-224-2244 Sir Charles Gairdner Hospital – Perth, Perth, Western Australia, 6009, Australia; Recruiting Guy A. Van Hazel, MD 61-89-481-3072 guy.vanhazel@health.wa.gov.au