R-CHOP-B Bevacizumab for Diffuse Large B Cell Lymphoma

This study has been terminated.

First Received on November 10, 2008.  
Last Updated on April 12, 2012  
History of Changes
This Clinical Trial Sponsored By: Royal Marsden NHS Foundation Trust
Collaborator: Hoffmann-La Roche
Information provided by (Responsible Party): Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00788606
 

Purpose for Clinical Trial

This study evaluates the use of the standard treatment R-CHOP plus the anti-VEGF drug, bevacizumab and whether this treatment is feasible in patients with stage II, III and IV diffuse large B cell lymphoma (DLBCL).

Condition Study Intervention Clinical Trial Phase
Non-Hodgkin’s Lymphoma
B-cell Lymphoma
Drug: bevacizumab, Rituximab Phase 2

Study Type: Study Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Study Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Feasibility Study of R-CHOP Plus Bevacizumab in Patients With Diffuse Large B Cell Lymphoma (DLBCL)

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Rituximab
Bevacizumab

U.S. FDA Resources

Further study details as provided by Royal Marsden NHS Foundation Trust:

Primary Outcome Measures For Clinical Trial:

  • The primary endpoint of this study is cardiac and bevacizumab-specific toxicity. Toxicities will be evaluated according to the NCI Common Toxicity Criteria for Adverse Events v3.0 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures For Clinical Trial:

  • Response rates, failure free survival, and overall survival will be evaluated and are secondary endpoints [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: May 2008
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: bevacizumab and Rituximab

This study evaluates the feasibility using the anti-VEGF drug, bevacizumab, in combination with the standard treatment Rituximab in patients with stage II, III and IV diffuse large B cell lymphoma (DLBCL)
Drug: bevacizumab, Rituximab

6 cycles of treatment. Bevacizumab at a dose of 15 mg/kg, diluted in normal saline will be administered as a intravenous infusion over 30 to 90 minutes on Day 1 of each cycle. Rituzimab 375 mg/m2 is given as a intravenous infusion after the administration of prednisolone and before the other cytotoxic drugs on Day 1 of each cycle.

Detailed Description:

Non-Hodgkin’s lymphoma is increasing in incidence with more than 287,000 cases world-wide and 9000 cases in UK diagnosed each year. DLBCL is the most frequently occurring NHL, constituting approximately 31% of all non-Hodgkin’s lymphomas.

Rituximab-CHOP chemotherapy has shown clinical efficacy and is regarded as standard treatment in patients with DLBCL. NICE has recently approved the use of rituzimab in combination with CHOP for all newly diagnosed patients with DLBCL stage II-IV.

Angiogenesis plays an important role in the pathophysiology of both solid tumours and hematologic malignancies. Vascular endothelial growth factor (VEGF) is the most important pro-angiogenic factor involved in normal and pathologic angiogenesis and studies have also implicated VEGF in lymphomagenesis. Elevated VEGF gene expression correlates with diffuse large B cell lymphoma subtypes of poor prognosis on microarray analysis. In patients with lymphoma, high circulating serum VEGF levels have been strongly associated with poor clinical outcomes independent of other predictive factors.

Bevacizumab is a humanized monoclonal antibody that binds to VEGF thus preventing binding to its receptors thus inhibiting the downstream pathways dependent on receptor stimulation. Bevacizamab has shown activity in solid tumours (colorectal, renal, breast and non-small cell lung cancer) and early results suggest that the combination of R-CHOP plus bevacizamab is feasible in patients with non Hodgkin’s lymphoma.

Patients will be treated with a minimum of 6 cycles of treatment. A further 2 cycles, to a total of 8 cycles, may be administered if continuing response to treatment has been documented but residual disease is still detectable on restaging after 6 cycles. Each cycle of treatment is 21 days.

Follow up – a) Clinic visit with physical examination at 3, 6, 9, 12, 18 and 24 months after completion of R-CHOP-B, then annually.

b) CT scan of chest, abdomen and pelvis at 3 months and 1 year after finishing treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years.
  • Histological proven diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) according to the World Health Organization classification including morphological variants. The B cell nature of the proliferation must be verified by the positivity with an anti-CD20 antibody. All histology will be reveiwed by a central Lymphoma Trials Office pathology panel.
  • No previous chemotherapy, radiotherapy or other investigational drug for this indication.
  • Stage II, III and IV disease.
  • WHO performance status 0<2.
  • Adequate bone marrow function with platelets > 100×109/l: neutrophils > 1.5×109/l at the time of study entry unless attributed to bone marrow infiltration by lymphoma.
  • Serum creatinine < 150μmol/l , serum bilirubin < 35μmol/l and transaminases < 2.5 x upper limit of institutional normal range unless attributed to lymphoma.
  • Normal MUGA or echocardiogram without any areas of abnormal contractility. Patients must have an acceptable left ventricular ejection fraction (LVEF) > 50%.
  • No current uncontrolled medical condition.
  • No active malignant disease other than basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix in the last 10 years.
  • Adequate contraceptive precautions for all patients of childbearing potential.
  • Written, informed consent.

Exclusion Criteria:

  • T-cell lymphoma or transformed follicular lymphoma.
  • Previous history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed who have a large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included.
  • Past history of heart failure or uncontrolled angina pectoris.
  • Central nervous system, meningeal involvement or cord compresssion by the lymphoma
  • Cardiac contra-indication to doxorubicin (abnormal contractility on echocardiography or nuclear medicine examination[MUGA])
  • Neurological contra-indication to vincristine (e.g pre-existing diabetic neuropathy).
  • Any other serious active disease
  • General status that does not allow the administration of 8 courses of CHOP according to the investigator
  • Positive serology for HIV, Hepatitis B or Hepatitis C
  • Medical or psychiatric conditions that compromise the patient’s ability to give informed consent
  • Bevacuzumab related criteria:

    • No major surgery, major trauma or open biopsy within 28 days prior to study entry. Patients requiring insertion of central venous access for treatment (e.g due to poor venous access) should have the procedure performed at least 2 days before starting treatment.
    • No serious, non-healing would, ulcer or bone fracture.
    • Absence of obvious risk of requiring emergency surgery after com

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