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Phase I-II Study of Low Dose CdA Combined With Valproic Acid (VPA) in Previously Treated B-cell Chronic Lymphocytic Leukemia (CLL) Patients

Phase 1/Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia

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Trial Information

Phase I-II Study of Low Dose CdA Combined With Valproic Acid (VPA) in Previously Treated B-cell Chronic Lymphocytic Leukemia (CLL) Patients

Inclusion Criteria:

- B-cell Chronic Lymphocytic Leukemia (CLL)

- Patients must have intermediate or high-risk categories of the modified 3-stage Rai
and Binet staging

- 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 months 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 Chronic Lymphocytic
Leukemia. Patients may have received any of the following prior treatment regimens:
fludarabine-containing combinations, alemtuzumab single agent or combination,
rituximab combinations, chlorambucil, cyclophosphamide +/- prednisone, or other forms
of immunotherapy…

- Patients must have adequate organ function:

- Neutrophils > 500/mm³

- Platelets > 50.000/mm³

- Creatinine clearance (measured or calculated) > 40 ml/min

- Age > 18 years

- Patient's ECOG performance status must be 0-2

- Patient's written informed consent

- Life expectancy > 6 months

Exclusion Criteria:

- Patients having received Valproic Acid (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

- Cumulative Illness rating Scale (CIRS) > 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

- Central Nervous System 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 hours 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

- 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 New York Heart Association 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: Human Immunodeficiency Virus, 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the tolerability of VPA in combination with low dose CdA in patients with advanced B-CLL

Outcome Time Frame:

6 months on average

Safety Issue:


Principal Investigator

Eric Van Den Neste, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cliniques universitaires Saint-Luc


Belgium: Federal Agency for Medicinal Products and Health Products

Study ID:




Start Date:

December 2010

Completion Date:

April 2013

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • CLL previously treated
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid