Clinical trial NCT00285103: SPC2996 in Chronic Lymphocytic Leukaemia
Official title: An Open-labelled, International, Multicenter, Dose Escalating, Phase I/II Study of SPC2996,an LNA Antisense Molecule Against Bcl-2, in Patients With Relapsed or Refractory Chronic Lymphocytic Leukaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Antisense, mRNA antagonist, Bcl-2, CLL
Lead sponsor: Santaris Pharma A/S
Sponsor class: INDUSTRY
First posted: 2006-02-01
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether SPC2996 is effective and safe in the treatment of Chronic Lymphocytic Leukaemia (CLL)

Detailed description: Chronic Lymphocytic Leukaemia (CLL) is the most common leukaemia in adults in the US and most of Western Europe. Many patients suffering from CLL have tumour cells expressing high amounts of Bcl-2 protein. Since over expression of Bcl-2 inhibits apoptosis, it is possible that this gene participates in the pathogenesis of CLL. By lowering the Bcl-2 protein in these tumour cells the cells may go into apoptosis due to changed balance in pro- and anti apoptotic proteins and thereby it might be possible to induce a tumour response.

The study is an open-labelled, international, multicenter, dose escalating phase I/II study where patients receive 6, 3, 2 or 1 dose(s) of SPC2996, a LNA antisense molecule against Bcl-2, over a period of up to 2 weeks, and are followed for 6 months.

Eligibility criteria: Inclusion Criteria:

* patients with relapsed or refractory Chronic Lymphocytic Leukaemia requiring therapy
* screening blood sample must show circulating lymphocyte count of more then 5 x 109/L and circulating lymphocytes expressing the phenotype CD5+CD20+CD23+.
* The PCR Bcl-2 m-RNA level must be positive
* the patients must be 18 years or older and have given informed consent.

Exclusion Criteria:

* previous treatment with rituximab, alemtuzumab or autologous stem cell transplantation within 6 months prior to Visit 1 or allogeneic stem cell transplantation at any time
* patients that received anti-cancer therapy, glucocorticoids or radiotherapy within 4 weeks prior to Visit 1 and patients with known or suspected transformation of CLL

Primary outcomes:
measure: Change in Bcl-2 m-RNA levels
timeFrame: from Day 0 to Day 13
Secondary outcomes:
measure: Change in Bcl-2 protein expression. Change in Bcl-2 m-RNA levels (and other parameters)
timeFrame: from Day 0 to Day 14 and during study respectively
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center, Univ. of Iowa
state: Iowa
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: KAS Herlev
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Lyon
country: France
facility: Service d'HématologieCentre Hospitalier Lyon-Syd
state: Cedex
city: Lille
country: France
facility: Bruno Cazin
city: Lyon
country: France
facility: Mauricette Michellet
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: MRC Toxicology Unit, University of Leicester
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Centre Hospitalier Lyon Sud, Lyon, France
name: Betrand Coiffier, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: