Clinical trial NCT00971763: Gemcitabine Hydrochloride, Cyclophosphamide, Vincristine Sulfate, Prednisolone, and Rituximab in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage I adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2009-09-04
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Overall response rate
timeFrame: End of treatment
Secondary outcomes:
measure: Toxicity
timeFrame: End of treatment
measure: Progression-free survival
timeFrame: Not specified in protocol
measure: Overall survival
timeFrame: Not specified in protocol
Other outcomes:
Locations:
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Cancer Research UK and University College London Cancer Trials Centre
state: England
Study officials:
affiliation: Cancer Research UK
name: Paul Fields, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunnningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. doi: 10.1200/JCO.2013.49.7586. Epub 2013 Nov 12.