Feasibility study of R-CHOP plus bevacizumab in patients with diffuse large B cell lymphoma (DLBCL) - R-CHOP-B

Phase 1

• Conditions: Previously untreated diffuse large B-cell non-Hodgkin's lymphoma

• Registration Number: EUCTR2006-003844-41-GB
• Lead Sponsor: Royal Marsden NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-02-12
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

a) Age at least 18 years.
b) Histological proven diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) according to the current World Health Organization classification20 including all morphological variants. The B cell nature of the proliferation must be verified by the positivity with an anti-CD20 antibody. All histology will be reviewed by a central Lymphoma Trials Office pathology panel.
c) No previous chemotherapy, radiotherapy or other investigational drug for this indication.
d) Stage II, III and IV disease
e) WHO performance status 0<2.
f) Adequate bone marrow function with platelets > 100x109/l; neutrophils > 1.5x109/l at the time of study entry unless attributed to bone marrow infiltration by lymphoma.
g) Serum creatinine < 150umol/l, serum bilirubin < 35umol/l and transaminases < 2.5x upper limit of institutional normal range unless attributed to lymphoma.
h) Normal MUGA or echocardiogram without any areas of abnormal contractility. Patients must have an acceptable left ventricular ejection fraction (LVEF) of at least 50%.
i) No concurrent uncontrolled medical condition.
j) 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.
k) Life expectancy > 3 months.
l) Adequate contraceptive precautions for all patients of childbearing potential
m) Written, informed consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

a) Lymphomatous involvement of, or lymphoma arising in the gastrointestinal tract.
b)T-cell lymphoma or transformed follicular lymphoma.
c) Previous history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed with an indolent lymphoma, who have diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included.
d) Past history of heart failure or uncontrolled angina pectoris.
e) Central nervous system, meningeal involvement or cord compression by
lymphoma.
f) Absence of clinically significant (i.e. active) cardiovascular disease e.g. cerebrovascular accidents (< 6 months prior to randomization), any myocardial infarction (< 1 year prior to randomization), uncontrolled hypertension while receiving chronic medication, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication abnormal contractility on echocardiography or nuclear medicine examination [MUGA]). Cardiac contraindication to doxorubicin.
g) Neurological contra-indication to vincristine (e.g. pre-existing diabetic neuropathy).
h) Any other serious active disease.
i) General status that does not allow the administration of 8 courses of CHOP according to the investigator.
j) Positive serology for HIV, Hepatitis B or Hepatitis C
k) Medical or psychiatric conditions that compromise the patient’s ability to give informed
consent.
l) Bevacizumab 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 wound, ulcer, or bone fracture
•Absence of obvious risk of requiring emergency surgery after commencement of study treatment, such as impending bowel obstruction
•No recent history of any active gastrointestinal inflammatory condition such as peptic ulcer disease, diverticulitis or inflammatory bowel disease. If patients have a known diagnosis of any of the above, evidence of disease control is required by negative endoscopy within the past 28 days
•No evidence of bleeding diathesis or coagulopathy
•No recent commencement of full dose oral anticoagulation (warfarin), unless stable and within therapeutic range for at least 10 days.
•No thrombolytic therapy within 10 days prior to commencement of study treatment
•No chronic, daily treatment with high-dose aspirin (> 325mg/day) or nonsteroidal anti-inflammatory medications (those known to inhibit platelet function at doses used to treat chronic inflammatory diseases)
•No chronic treatment with corticosteroids (dose of = 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids)
•No known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies or to any excipients of bevacizumab formulation, or to any other components of the study drugs
•No proteinuria at baseline as defined by >1g of protein/24 hr by a 24-hour urine collection

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified