Eltrombopag in Thrombocytopenic Chronic Lymphocytic Leukemia (CLL) Patients (CLL2S Study of GCLLSG)

NCT01397149 | Terminated Phase 1 DMC

• 2 other identifiers: CLL2S2010-023022-20
• Study Type: interventional
• Target: 4
• Locations: 2 countries
• Sites: 10

Brief Summary

The aim of this study is to find the appropriate dose of eltrombopag in thrombocytopenic CLL patients, that shortens the duration of the thrombocytopenia and achieves platelet count of ≥ 100/nl prior to the start of chemotherapy containing alkylating agents and/or Purine Analogues.

Conditions

Chronic Lymphocytic Leukemia; Thrombocytopenia

Keywords

Chronic lymphocytic leukemia; Thrombocytopenia; Alkylating agents; Purine derivatives; TPO receptor agonist

Outcome Measures

Primary Outcomes (1)

• Change in platelet count

  Time points of assessment: 1 wk before treatment; 2-3 times/wk during treatment; 30d after end of treatment Treatment duration: * Phase I: Two weeks * Phase II: Eltrombopag is given as concomitant treatment to chemotherapy, with a max. duration of max. 6 cycles of 28 days each. The exact schedule of Eltrombopag administration will be determined after evaluation of Phase I results.

  up to 7 months

Secondary Outcomes (9)

• Adverse events

  up to 8 months

• Change in vital signs

  up to 7 months

• Change in clinical laboratory parameters

  up to 7 months

• Bleeding events

  up to 7 months

• Number of required platelet transfusions

  up to 7 months

Study Arms (2)

Eltrombopag

EXPERIMENTAL

In phase II, patients will be randomized (2:1 eltrombopag : placebo) to receive either eltrombopag or placebo to explore the efficacy and confirm the safety of the identified eltrombopag dose from Phase I.

Drug: Eltrombopag

Film coated tablet

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

Dosage form, frequency and duration exactly as experimental arm.

Film coated tablet

Eltrombopag DRUG

Phase I: Single arm dose-escalation trial part, to test 4 doses of eltrombopag (75mg, 150mg, 225mg, 300mg) to find the appropriate, feasible dose to achieve a durable increase in platelet count (≥100,000/µl). Eltrombopag will be administered once daily at the respective dose level for 2 weeks (unless platelet counts rise to \> 400,000/µl). Phase II: Patients will be randomized (2:1 eltrombopag : placebo) to explore the efficacy and confirm the safety of the identified dose level from Phase I. Eltrombopag/placebo will be administered before starting each cycle (and possibly following chemotherapy treatment depending on data from phase I), and will continue during all cycles of treatment until subjects finish chemotherapy (alkylating agents and/or purine analogue-based therapy). The schedule and days of eltrombopag dosing in Phase II will be determined based on data analyzed from Phase I.

Also known as: Revolade, Promacta

Eltrombopag

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of CLL (based immunophenotyping performed at the central reference laboratory of the GCLLSG in Cologne)
• Platelet count \<50 000/μl at time of screening (measured and confirmed twice)
• Patient is planned to receive alkylating agents and/or fludarabine-based therapy as 2nd or higher-line treatment
• ECOG Performance Status of 0-2
• Age \>= 18 years
• Signed written informed consent, according to ICH-GCP, and national/local regulation, prior to performing any study-specific procedures
• Negative pregnancy test and willingness to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment (adequate: oral contraceptives, intrauterine device or barrier method in conjunction with spermicidal jelly).
• Able to understand and comply with protocol requirements and instructions and intend to complete the study as planned.
• Adequate renal function (creatinine must not exceed the upper limit of normal (ULN) reference range by more than 50%) at study entry
• Adequate liver function: bilirubin £ 1.5 times the upper limit of normal. ALT or AST \<= 3 times the upper limit of normal without liver involvement with CLL and \<= 5 times the upper limit of normal in case of the liver involvement with CLL
• Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range with no history of hypercoagulable state
• Total albumin must not be below the lower limit of normal (LLN) by more than 20%.

You may not qualify if:

• Thrombocytopenia that is primarily caused by ITP
• Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of last fludarabine and/or bendamustine based therapy. NOTE: Subjects refractory to rituximab monotherapy as last therapy are permitted
• No prior therapy for CLL
• Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy \>100mg equivalent to hydrocortisone, or chemotherapy
• Platelet count \> 50 000/μl at screening
• Richter's transformation
• CNS involvement of B-CLL
• Active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
• Past or current malignancy other than CLL (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless tumor was successfully treated with curative intent at least 2 years prior to trial entry
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months, congestive heart failure, etc.
• History of significant cerebrovascular disease
• Recurring venous thrombosis or pulmonary embolism
• Glucocorticoids unless given in doses \<= 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoids) and for exacerbations other than CLL (e.g. asthma)
• Known HIV positivity
• Active hepatitis B, C

Sponsors & Collaborators

• University of Ulm: lead
• GlaxoSmithKline: collaborator
• German CLL Study Group: collaborator
• WiSP Wissenschaftlicher Service Pharma GmbH: collaborator

Study Sites (10)

Medizinische Universität Wien, Innere Medizin I, Abt. Hämatologie und Hämastaseologie

Vienna, 1090, Austria

Location

Universitätsklinikum Köln; Klinik I für Innere Medizin

Cologne, 50924, Germany

Location

Universitätsklinikum Carl Gustav Carus Med. Klinik und Poliklinik I

Dresden, 01307, Germany

Location

Gemeinschaftspraxis für Innere Medizin, Hämatologie und Internistische Onkologie

Erlangen, 91052, Germany

Location

Universitätsklinikum; Klinik für Hämatologie

Essen, 45147, Germany

Location

Klinikum Frankfurt (Oder) Medizinische Klinik I

Frankfurt (Oder), 15236, Germany

Location

Universitätsklinikum Schleswig-Holstein, II. Medizinische Klinik und Poliklinik im Städtischen Krankenhaus

Kiel, 24116, Germany

Location

Onkologische Schwerpunktpraxis Leer-Emden

Leer, 26789, Germany

Location

Städtisches Klinikum München GmbH, Klinikum Schwabing, Klinik für Hämatologie, Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin

München, 80804, Germany

Location

Universitätsklinikum Ulm, Medizinische Klinik III

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Thrombocytopenia

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Platelet Disorders; Cytopenia

Study Officials

• Stephan Stilgenbauer, Prof. Dr.

  Universitätsklinikum Ulm, Medizinische Klinik III

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: June 30, 2011
• First Posted: July 19, 2011
• Study Start: October 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2014
• Last Updated: May 28, 2015

Record last verified: 2015-05

Locations

AU (1); DE (9)