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

University College London (UCL)

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: prednisolone; Drug: cyclophosphamide; Drug: vincristine sulfate; Biological: rituximab; Drug: gemcitabine hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT00971763

EU-20951

CDR0000644293

UCL/05/154 (Other Identifier)

2005-003888-23 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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62 participants in 1 patient group

R-GCVP

Experimental group

Description:

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

Treatment:

Drug: gemcitabine hydrochloride

Biological: rituximab

Drug: prednisolone

Drug: vincristine sulfate

Drug: cyclophosphamide