Gemcitabine Hydrochloride, Cyclophosphamide, Vincristine Sulfate, Prednisolone, and Rituximab in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

Sponsor

University College, London (Other)

Overall Status

Completed

CT.gov ID

NCT00971763

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

15.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving more than one drug (combination chemotherapy) together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying giving gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone together with rituximab to see how well it works in treating patients with newly diagnosed diffuse large B-cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: gemcitabine hydrochloride Drug: prednisolone Drug: vincristine sulfate	Phase 2

Detailed Description

OBJECTIVES:

To determine whether rituximab, in combination with non-cardiotoxic chemotherapy comprising gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone, is efficacious in a group of patients who are unfit for CHOP chemotherapy.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8; cyclophosphamide IV, vincristine sulfate IV, and rituximab IV on day 1; and oral prednisolone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Multicentre Trial of Gemcitabine, CVP, and Rituximab (R-GCVP) for the Treatment of Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma, Considered Unsuitable for R-CHOP Chemotherapy

Study Start Date :

Mar 1, 2006

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: R-GCVP Up to 6 x 21 day cycles of R-GCVP: Gemcitabine 750mg/m^2 days 1 & 8 (increasing to 875mg/m^2 for cycle 2 & 1g/m^2 for subsequent cycles if tolerated satisfactorily) Cyclophosphamide 750mg/m^2 day 1 Vincristine 1.4mg/m^2 day 1 (capped at 2mg) Prednisolone 100mg/day days 1-5 Rituximab 375mg/m^2 day 1 Neulasta 6mg day 9	Biological: rituximab Drug: cyclophosphamide Drug: gemcitabine hydrochloride Drug: prednisolone Drug: vincristine sulfate

Arm

Intervention/Treatment

Experimental: R-GCVP

Up to 6 x 21 day cycles of R-GCVP: Gemcitabine 750mg/m^2 days 1 & 8 (increasing to 875mg/m^2 for cycle 2 & 1g/m^2 for subsequent cycles if tolerated satisfactorily) Cyclophosphamide 750mg/m^2 day 1 Vincristine 1.4mg/m^2 day 1 (capped at 2mg) Prednisolone 100mg/day days 1-5 Rituximab 375mg/m^2 day 1 Neulasta 6mg day 9

Biological: rituximab

Drug: cyclophosphamide

Drug: gemcitabine hydrochloride

Drug: prednisolone

Drug: vincristine sulfate

Outcome Measures

Primary Outcome Measures

Overall response rate [End of treatment]

Secondary Outcome Measures

Toxicity [End of treatment]
Progression-free survival [Not specified in protocol]
Overall survival [Not specified in protocol]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed CD20-positive diffuse large B-cell non-Hodgkin lymphoma (DLBCL) according to the current WHO classification, including all morphological variants
Newly diagnosed disease
Bulky stage IA-IV disease
No non-bulky stage IA disease
Measurable disease
Not eligible for CHOP chemotherapy due to impaired cardiac function
Cardiac status that does not allow the administration of 8 courses of R-CHOP chemotherapy, as defined by 1 of the following criteria:
Ejection fraction less than 50% as assessed by either ECHO or MUGA scan
NYHA class III-IV
No high-grade transformation of low-grade lymphoma
No symptomatic central nervous system or meningeal involvement by the lymphoma
No AIDS-related lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-3
Life expectancy > 3 months
Platelet count > 100 x 10^9/L
WBC > 3 x 10^9/L
Neutrophils > 1.5 x 10^9/L (unless elevated level attributed to bone marrow infiltration by lymphoma)
Serum bilirubin < 50 μmol/L
Transaminases < 2.5 times upper limit of normal (unless elevated level attributed to lymphoma)
Glomerular filtration rate > 30 mL/min
Not pregnant or nursing
Fertile patients must use effective contraception
No other concurrent uncontrolled medical condition
No active malignant disease, other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix, within the past 10 years
No positive serology for HIV
No medical or psychiatric conditions that compromise the patient's ability to give informed consent

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, radiotherapy, or other investigational drug for this indication

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England	United Kingdom	BN2 5BE
2	Leeds General Infirmary	Leeds	England	United Kingdom	LS1 3EX
3	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
4	Cancer Research UK and University College London Cancer Trials Centre	London	England	United Kingdom	SE1 9RT