Phase III trial of combined immunochemotherapy with Fludarabine, Cyclophosphamide and Rituximab (FCR) versus Bendamustine and Rituximab (BR) in patients with previously untreated chronic lymphocytic leukemia - CLL10

Phase 1

• Conditions: patients (age 18 years or older) with chronic lymphocytic leukemia: Stage Binet C or stage Binet B and A requiring treatment; MedDRA version: 14.0Level: LLTClassification code 10009310Term: CLLSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2007-007587-21-CZ
• Lead Sponsor: GCLLSG - Dept. of Internal Medicine I, University Hospital Cologne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-10
• Last Update Posted: 26 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

1. 18 years of age or older.
2. Confirmed diagnosis of B-CLL.
3. Stage Binet C or stage Binet B and A requiring treatment. Requiring treatment is defined as:
a) Binet stage B or Binet A plus at least one of the following symptoms:
- B-Symptoms (night sweats, weight loss >= 10% within the previous 6 months, fevers > 38°C or 100.4°F for >= 2 weeks without evidence of infection) or constitutional symptoms (fatigue)
- progressive lymphocytosis (lymphocytosis is defined as peripheral lymphocyte count > 5 x 10.9 (increase > 50% over a 2-month period or doubling of peripheral lymphocyte count < 6 months)
- evidence of progressive marrow failure as manifested by the development / worsening of anemia and/or thrombocytopenia
- massive, progressive or painful splenomegaly or hypersplenism
- massive lymph nodes or lymph node clusters (> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
b) Binet stage A with severe B-Symptoms (night sweats, weight loss >=10% within the previous 6 months, fevers > 38°C or 100.4°F for ³ 2 weeks without evidence of infection).
4. World Health Organization performance status of 0-2.
5. Life expectancy> 6 months.
6. Adequate liver function as indicated by a total bilirubin, AST, and ALT =2 the institutional ULN value, unless directly attributable to the patient’s tumor.
7. Willingness of fertile Male and female patients to use an highlyeffective contraceptive method with a Pearl-Index < 1 (such as implants, injectables, oral contraceptives in combincation with an other contraceptive method, some IUDs, sexual abstinence or vasectomised partner) while on study treatment and for a minimum of six months following study therapy
8. Signed, written informed consent.
9. Patient is a) male b) female and ³ 2 years after the onset of menopause c) female and < 2 years after the onset of menopause and has a negative serum pregnancy test one week prior treatment.
10. Negative serological Hepatitis B test, negative testing of Hepatitis C RNA, negative HIV test within 6 weeks prior to registration.
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. CIRS-Score > 6 or a single score of 4 for one organ category
2. Patients with a 17p deletion detected by FISH (these patients will be treated within the CLL2O or CLL2L protocol of the GCLLSG)
3. Creatinine clearance <70ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24h-urine collection. Creatinine clearance is to be calculated only in patients with serum creatinine > and = 1,1 mg/dl.
4. Any prior chemotherapy and/or radiotherapy and/or immunotherapy, except for prednisolone treatment administered due to very high lymphocyte counts immediately before first FCR or BR treatment.
5. Patients who have progressed with more aggressive B-cell cancers such as Richter’s syndrome.
6. Active secondary malignancy requiring treatment (except basal cell carcinoma or malignant tumour curatively treated by surgery).
7. History of anaphylaxis following exposure to monoclonal antibodies or any of the study drugs.
8. Active bacterial, viral or fungal infection.
9. Medical condition requiring prolonged use of oral corticosteroids (> 1 month).
10. Cerebral dysfunction, legal incapacity.
11. Pregnant or nursing women, fertile men or women of childbearing potential not using adequate contraception.
12. Any circumstance at the time of study entry that would preclude completion of the study or the required follow-up.
13. Participation in any other clinical trial

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: the progression free survival (PFS);Secondary Objective: the duration of remission<br>the event free survival (EFS)<br>the overall survival (OS)<br>MRD, complete response rates and partial remission rates<br>response rates and survival times in biological subgroups<br>rates of toxicities<br>quality of life;Primary end point(s): the progression free survival (PFS).