Safety and Tolerability Open Label Dose Escalation Study of Acadesine in B-CLL Patients

This study has been completed.
Sponsor:
Collaborator:
Nexus Oncology Ltd
Information provided by:
Advancell - Advanced In Vitro Cell Technologies, S.A.
ClinicalTrials.gov Identifier:
NCT00559624
First received: November 15, 2007
Last updated: May 9, 2011
Last verified: May 2011
  Purpose

The main aim of this study is to test the safety of acadesine in patients with B-CLL and see what effects it has on patients and their leukaemia. The study also aims to examine the way acadesine is processed by the body. The study will look at the effects of acadesine in the body and the concentration of the drug and its main by-product (ZMP) in the blood to determine the dose and the frequency of dosing that is likely to be the most effective.


Condition Intervention Phase
Leukemia, B-Cell, Chronic
Drug: Acadesine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Open Label Dose Escalation Study to Investigate the Safety and Tolerability of Acadesine in Patients With B-cell Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Advancell - Advanced In Vitro Cell Technologies, S.A.:

Primary Outcome Measures:
  • adverse event and serious adverse events(incidence, causality, severity), local tolerability (including liver enzymes, blood glucose and uric acid) and vital signs. [ Time Frame: up to and including Day 22 follow up visit ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: December 2007
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Acadesine
    For part I of the study one 4 hour intravenous infusion will be given. In part II upto five 4 hour intravenous infusions will be given over 20 days.
    Other Name: Acadra
  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • B-CLL patients with refractory or relapsed disease who have received one or more (≥ 1) prior lines of treatment which must have included either a fludarabine based regimen or an alkylator based regimen. Refractoriness is defined as any patient who has failed to achieve a CR, nPR or PR according to the National Cancer Institute (NCI) working group guidelines for CLL. Fludarabine refractoriness will also include patients who achieved a CR, nPR or PR of ≤ 6 months duration.
  • Diagnosis of B-CLL according to NCI Working Group Criteria.
  • Have an elevated B-cell count of ≥ 5000/mm3.
  • Have a T-cell count ≥ 200/mm3.
  • ECOG Performance Status ≤ 2.
  • Have a life expectancy of at least 3 months.
  • Age ≥ 18 years, of either gender.
  • Have given written informed consent, prior to any study related procedure not part of the patient's normal medical care
  • Receive allopurinol prophylaxis for hyperuricaemia.

Exclusion Criteria:

  • Patients who, in the opinion of the Investigator, need immediate treatment with proven chemotherapy and/or immunotherapy, and/or transplantation.
  • Have B-CLL with central nervous system involvement.
  • Have participated in any other investigational drug study or have undergone an experimental therapeutic procedure considered to potentially interfere with the study in the 30 days preceding Day 1.
  • Have received chemotherapy or radiotherapy treatment in the 30 days preceding Day 1.
  • Require oral or parenteral steroids with the exception of inhaled steroids or low-dose oral steroids (<10mg prednisolone per day or equivalent) for an indication other than B-CLL.
  • Have a serious medical or psychiatric condition that could, in the Investigator's opinion, potentially interfere with their treatment and/or participation in the study.
  • Have uncontrolled diabetes mellitus
  • Have a history of gout.
  • Have a serious concomitant disease including:

    • Significant cardiac disease - New York Heart Association Classes III or IV or have suffered a myocardial infarction in the last 6 months.
    • Chronic pulmonary obstructive disease with hypoxemia.
    • Clinically active auto-immune disease.
    • Active infection such as tuberculosis, CMV (Cytomegalovirus).
  • Any secondary malignancy requiring active treatment (except hormonal therapy).
  • Have inadequate bone marrow reserve: neutrophils < 1.0 x 109/L, platelet count < 50 x 109/L (unsupported by transfusion), or coagulation abnormalities.
  • Have inadequate liver function: total bilirubin > 1.5 x upper limit of normal values (ULN), AST, ALT, or alkaline phosphatase > 2.5 x ULN.
  • Have inadequate renal function, defined by serum creatinine ≥ 1.5 x ULN, unless creatinine clearance is measured and found to be at least 60 mL/min.
  • Have serum uric acid levels outside the normal range.
  • Females of childbearing potential who are unwilling to employ adequate means of contraception (hormonal contraceptive, intrauterine device, diaphragm with spermicide or condom with spermicide) for the duration of the study and 30 days after the last acadesine administration.
  • Pregnant or lactating females.
  • Male patients who are not surgically sterile and who are unwilling to use a condom with spermicide for the duration of the study and for 3 months after the last acadesine administration.
  • Abuse of alcohol or other recreational drugs.
  • Known HIV or Hepatitis B (unless clearly due to vaccination) or C positive.
  • Known allergy to acadesine or any of its excipients.
  • Have undergone previous allogeneic stem cell transplant.
  • Transformation to Richter's syndrome or other aggressive B-cell malignancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559624

Locations
Belgium
Hematology Department, ZNA Stuivenberg
Antwerpen, Belgium
Cliniques universitaires Saint-Luc Haematology Dept
Brussels, Belgium
Hematology Department UZ Gasthuisberg
Leuven, Belgium
France
Hôpital Avicenne
Bobigny, France
Service des maladies du sang Hôpital HURIEZ, CHRU
Lille, France
Spain
Hematologia Clinica, Institut Catala d'Oncologia
Barcelona, Spain, 08907
Hospital Madrid Nortesanchinarro
Madrid, Spain, 28050
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Advancell - Advanced In Vitro Cell Technologies, S.A.
Nexus Oncology Ltd
Investigators
Principal Investigator: Eric Van Den Neste, MD Cliniques universitaires Saint-Luc
  More Information

No publications provided

Responsible Party: Clara Campàs i Moya, PhD, Advancell - Advanced In Vitro Cell Technologies, S.A.
ClinicalTrials.gov Identifier: NCT00559624     History of Changes
Other Study ID Numbers: ATH001-CLN01
Study First Received: November 15, 2007
Last Updated: May 9, 2011
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency of Medicines

Keywords provided by Advancell - Advanced In Vitro Cell Technologies, S.A.:
safety
tolerability
dose-escalation

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014