Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005325

Trial Description

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Title

A Two-part Study to Assess the Safety and Preliminary Efficacy of Givinostat in Patients With Polycythemia Vera

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

This is a two-part, multicenter, open label, non-randomized, phase Ib/II study to assess the
safety and tolerability, Maximum Tolerated Dose and preliminary efficacy of Givinostat in
patients with JAK2V617F positive Polycythemia Vera. Part A is the dose finding part while
Part B is assessing the preliminary efficacy. Patients will be enrolled either in Part A or
Part B and transition from one part to the other is not allowed.

Eligible patients for this study will have a confirmed diagnosis of Polycythemia Vera
according to the revised World Health Organization criteria. Only if the enrolment in Part A
is slow (i.e. < 5 patients enrolled in 3 months), eligibility for this part of the study may
be expanded to all patients with chronic myeloproliferative neoplasms.

Study therapy will be administered in 28 day cycles (4 weeks of treatment). Disease response
will be evaluated according to the European LeukemiaNet criteria after 3 and 6 cycles (i.e.
at weeks 12 and 24, respectively) of treatment with Givinostat for both parts of the study.
All phlebotomies performed in the first 3 weeks of treatment will not be counted to assess
the clinico-haematological response.

The study will last up to a maximum of 24 weeks of treatment. However, after completion of
the trial, all patients achieving clinical benefit will be allowed to continue treatment
with Givinostat (at the same dose and schedule) in a long-term study.

Safety will be monitored at each visit throughout the entire duration of the study.
Treatment will be administered on an outpatient basis and patients will be followed
regularly with physical and laboratory tests, as specified in the protocol; in case of
hospitalization, the treatment will be continued or interrupted according to the
Investigators' decision.

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Brief Summary in Scientific Language

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Organizational Data

  •   DRKS00005325
  •   2013/10/24
  •   2013/07/10
  •   no
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Secondary IDs

  •   2013-000860-27 
  •   NCT01901432  (ClinicalTrials.gov)
  •   DSC/12/2357/45  (Italfarmaco)
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Health Condition or Problem studied

  •   Polycythemia Vera
  •   D45 -  Polycythaemia vera
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Interventions/Observational Groups

  •   Drug: Givinostat
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
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Primary Outcome

- Part A: Maximum Tolerated Dose; time frame: 168 days (i.e. 6 cycles); Determination of the Maximum Tolerated Dose of Givinostat based on cycle 1 Dose Limiting Toxicity's.
- Part B: Preliminary efficacy after 3 cycles of treatment; time frame: 84 days (i.e. 3 cycles); Overall response rate - i.e. Complete Response and Partial Response - of Givinostat at the Maximum Tolerated Dose after 3 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet response criteria.
- Part A: Safety and tolerability; time frame: 168 days (i.e. 6 cycles); Safety and tolerability evaluated as following:
Number of patients experiencing adverse events;
Type, incidence, and severity of treatment-related adverse events.
- Part B: Safety and tolerability after 3 cycles of treatment; time frame: 84 days (i.e. 3 cycles); Safety and tolerability of Givinostat at the Maximum Tolerated Dose after 3 cycles evaluated as following:
Number of patients experiencing adverse events;
Type, incidence, and severity of treatment-related adverse events.

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Secondary Outcome

- Part A: characterization of pharmacokinetic; time frame: 84 and 168 days (i.e. clycles 3 and 6); Individual Givinostat concentrations tabulated by dose cohort along with descriptive statistics.
- Part B: characterization of pharmacokinetic; time frame: 168 days (i.e. 6 cycles); Individual Givinostat concentrations tabulated with descriptive statistics.
- Part A: preliminary efficacy after 3 and 6 cycles of treatment; time frame: 84 and 168 days (i.e. clycles 3 and 6); Overall response rate - i.e. Complete Response and Partial Response - of Givinostat at the Maximum Tolerated Dose after 3 and 6 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet response criteria.
- Part B: preliminary efficacy of Givinostat at the Maximum Tolerated Dose after 6 cycles.; time frame: 168 days (i.e. 6 cycles); Overall response rate - i.e. Complete Response and Partial Response - of Givinostat at the Maximum Tolerated Dose after 6 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet response criteria.
- Part B: safety and tolerability after 6 cycles; time frame: 168 days (i.e. 6 cycles); Safety and tolerability of Givinostat at the Maximum Tolerated Dose after 6 cycles evaluated as following:
Number of patients experiencing adverse events;
Type, incidence, and severity of treatment-related adverse events.

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Countries of Recruitment

  •   France
  •   Germany
  •   Italy
  •   Poland
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2013/10/31
  •   52
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. Patients must be able to provide informed consent and be willing to sign an informed
consent form;

2. Patients must have an age ≥18 years;

3. Patients must have a confirmed diagnosis of Polycythemia Vera according to the
revised World Health Organization criteria;

4. Patients must have mutated Janus Kinase 2 (mutation V617F) positive disease;

5. Patients must have an active/not controlled disease defined as

1. hematocrit ≥ 45% or hematocrit <45% in need of phlebotomy, and

2. platelet count > 400 x109/L, and

3. white blood cell count > 10 x109/L;

6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤
1 in Part A, ECOG performance status ≤ 2 in Part B within 7 days of initiating study
drug;

7. Female patient of childbearing potential has a negative serum or urine pregnancy test
within 72 hours of the first dose of study therapy;

8. Use of an effective means of contraception for women of childbearing potential and
men with partners of childbearing potential;

9. Adequate and acceptable organ function within 7 days of initiating study drug;

10. Willingness and capability to comply with the requirements of the study.

Note that if the enrolment in Part A is slow (i.e. < 5 patients enrolled in 3 months),
eligibility for this part of the study may be expanded to all patients with chronic
myeloproliferative neoplasms. In this case, the inclusion criteria 5 will be modified as
following only for Part A:

5. Patients must have an active/not controlled disease defined as:

1. Essential Thrombocythemia patients: Platelet count > 600 x109/L;

2. Myelofibrosis patients: no response according to European Myelofibrosis Network
criteria.

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Exclusion Criteria

1. Active bacterial or mycotic infection requiring antimicrobial treatment;

2. Pregnancy or nursing;

3. A clinically significant corrected QT interval prolongation at baseline;

4. Use of concomitant medications known to prolong the corrected QT interval;

5. Clinically significant cardiovascular disease including:

1. Uncontrolled hypertension despite medical treatment, myocardial infarction,
unstable angina within 6 months from study start;

2. New York Heart Association Grade II or greater congestive heart failure;

3. History of any cardiac arrhythmia requiring medication (irrespective of its
severity);

4. A history of additional risk factors for torsade de pointes;

6. Known positivity for human immunodeficiency;

7. Known active hepatitis B virus and/or hepatitis C virus infection;

8. Platelet count < 100 x109/L within 14 days before enrolment;

9. Absolute neutrophil count < 1.2x109/L within 14 days before enrolment;

10. Serum creatinine > 2 times the upper limit of normal;

11. Total serum bilirubin > 1.5 times the upper limit of normal except in case of
Gilbert's disease;

12. Serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 times the
upper limit of normal;

13. History of other diseases (including active tumours), metabolic dysfunctions,
physical examination findings, or clinical laboratory findings giving reasonable
suspicion of a disease or condition that contraindicates use of an investigational
drug or that might affect interpretation of the results of the study or render the
subject at high risk from treatment complications;

14. Prior treatment with a Janus Kinase 2 or Histone Deacetylase inhibitor or
participation in an interventional clinical trial for chronic myeloproliferative
neoplasms;

15. Systemic treatment for chronic myeloproliferative neoplasms other than aspirin/cardio
aspirin;

16. Hydroxyurea within 28 days before enrolment;

17. Interferon alpha within 14 days before enrolment;

18. Anagrelide within 7 days before enrolment;

19. Any other investigational drug or device within 28 days before enrolment;

20. Patient with known hypersensitivity to the components of study therapy.

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Addresses

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    • Italfarmaco
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  • start of 1:1-Block address scientific-contact
    • Paolo Bettica, MD, PhD 
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    • Paolo Bettica, MD, PhD 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   6
  •   2013/10/20
* This entry means the parameter is not applicable or has not been set.