Phase I-II study of low dose CdA combined with valproic acid (VPA) in previously treated B-cell chronic lymphocytic leukemia (CLL) patients. - VPA-CdA in C

Phase 1

• Conditions: •B-CLL, as defined by the NCIWG criteria •Patients must have intermediate or high-risk categories of the modified 3-stage Rai and Binet stagings; MedDRA version: 14.0Level: LLTClassification code 10008977Term: Chronic lymphocytic leukemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2010-019983-35-BE
• Lead Sponsor: Cliniques universitaires Saint Luc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-09
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 33

Inclusion Criteria

•B-CLL, as defined by the NCIWG criteria
•Patients must have intermediate or high-risk categories of the modified 3-stage Rai and Binet stagings
•Patient MUST have progressive or symptomatic disease as defined by any of the following conditions:
- Progressive lymphocytosis with a lymphocyte count increased > 50% over the last 2 month period or an anticipation of the doubling time in less than 6 months
- Progressive or symptomatic splenomegaly or hepatomegaly
- Progressive or symptomatic lymphadenopathy
- Evidence of progressive marrow failure as manifested by development or worsening of anemia and/or thrombocytopenia
- Presence of any B-symptoms: weight loss = 10% within the previous 6 months, fever > 38.0°C for = 2 weeks without evidence of infection, or night sweats without evidence of infection.
•Patient must have received one or more prior therapies for CLL. Patients may have received any of the following prior treatment regimens: fludarabine-containing combinations, alemtuzumab single agent or combination, rituximab combinations, chlorambucil, cyclophosphamide +/- prednisone, CVP, or other forms of immunotherapy…
•Patients must have adequate organ function:
Neutrophils > 500/mm³
Platelets > 50.000/mm³
Creatinine clearance (measured or calculated) > or = 40 ml/min
•Age > 18 years
•Patient’s ECOG performance status must be 0-2
•Patient’s written informed consent
•Life expectancy > 6 months

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

•Patients having received VPA within 3 months
•Previous, suspected or known hypersensitivity to VPA, or any of its derivatives
•Liver porphyria
•Epilepsy due to mitochondrial diseases
•Ongoing treatment with VPA-interacting drugs
•CIRS (Cumulative Illness rating Scale) > 6
•Prior allogenic or autologous bone marrow transplantation less than 12 months
•Patient having received any anticancer agents (chemotherapy, immunotherapy or targeted agents) within 4 weeks
•CNS involvement
•Concomitant disease requiring prolonged use of corticosteroids (> 1 month)
•Transformation into an aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma)
•Creatinine clearance < 40 ml/min calculated according to the formula of Cockcroft and Gault. Patients with a calculated creatinine clearance below 40 ml/min may be eligible if (1) a measured creatinine clearance (based on 24-h urine collection or other reliable method) is > 40 ml/min, or (2) a new calculation conducted after adequate hydration is > 40 ml/min.
•Any coexisting medical or psychological condition that would preclude participation to the required study procedures
•Patient with mental deficiency preventing proper understanding of the requirements of treatment
•Pregnancy, lactating woman, females of childbearing potential or male patient who are unwilling to use adequate contraception
•Clinically significant auto-immune cytopenia, Coombs-positive hemolytic anemia as judged by the treating physician
•Patients with a history of another malignancy in complete remission less than 2 years, except basal cell skin cancer, stage 0 (in situ) cervical carcinoma or tumor treated curatively by surgery.
•Any severe co-morbidities such as NYHA Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, or severe uncontrolled myocardiopathy, uncontrolled hypertension, severe chronic obstructive pulmonary disease with hypoxemia or uncontrolled diabetes mellitus.
•Active bacterial, viral or fungal infection
•Seropositivity for: HIV, hepatitis C or hepatitis B (unless clearly due to vaccination)
•Liver insufficiency
•Total bilirubin > 2 x the upper limit of normal (ULN)
•Prior history of severe hepatic or pancreatic disorder
•Alkaline phosphatases and aminotransferases (AST, ALT) > 2 x ULN

Study & Design

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