Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage
This is a phase II, multi-center study of pomalidomide in adult patients with PMF, SMF, and unclassifiable MPN showing at least grade 1 bone marrow fibrosis and requiring therapy. All patients will receive per oral pomalidomide on a daily basis.
First cohort (Before Amendment No. 1 ID 1-41):
Treatment starts with a phase of pomalidomide therapy with 2 mg per day. Individual dose reduction as outlined in the safety section is allowed. If no response was achieved (no complete remission (CR), partial response (PR), clinical improvement (CI) and no progressive disease according to the IWG-MRT criteria) after 3 months, prednisolone is added in a starting dose of 30 mg per day. In the absence of progressive disease, at least 6 months of treatment with pomalidomide is intended. In patients without disease progression after 6 months and those with response to treatment are intended to receive pomalidomide for at least 12 months. Additional antiproliferative treatment with hydroxyurea for leukocytosis (>20 x 109/l) and/or thrombocytosis (>750 x 109/l) and/or symptomatic splenomegaly in a starting dose of 2g/day with individual dose adjustment is allowed.
Second cohort (After Amendment No. 1 ID > 41):
To evaluate the relative impact of prednisolone to the objective response rate, a randomization has been integrated into the study concept. The addition of prednisolone is up-front randomized for the start of prednisolone either after 3 or 6 cycles of treatment with pomalidomide as single agent if no response occurred during this period. This results in the following treatment arms:
Treatment Arm A) Pomalidomide 0.5 mg per day + additional prednisolone at start of cycle 4 (day 85), in case no response was achieved until end of cycle 3.
Treatment Arm B) Pomalidomide 0.5 mg per day + additional prednisolone at start of cycle 7 (day 169), if no response was achieved until end of cycle 6.
Treatment for all patients starts with pomalidomide as single agent at a dose of 0.5mg per day. The addition of prednisolone will be initiated as randomized either at start of cycle 4 or start of cycle 7 (starting dose 30 mg per day). In the absence of progressive disease, at least 12 cycles of treatment with pomalidomide are intended.
Additional antiproliferative treatment with hydroxyurea for leukocytosis (>20 x 109/l) and/or thrombocytosis (>750 x 109/l) and/or symptomatic splenomegaly in a starting dose of 2g/day with individual dose adjustment is allowed.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multi-Center Phase II Study With Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage|
- Objective disease response, as defined by the IWG-MRT criteria for response in MF patients extended by the criterion RBC-transfusion independence (TI) [ Time Frame: one year ] [ Designated as safety issue: No ]
- Overall safety profile of pomalidomide characterized by type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during treatment [ Time Frame: one year ] [ Designated as safety issue: No ]Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0
- Event-free survival [ Time Frame: three years ] [ Designated as safety issue: No ]
- Relapse-free survival [ Time Frame: three years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: three years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Every patient will remain on treatment until disease progression for at least 12 cycles, withdrawal of patient's informed consent or the occurrence of unacceptable toxicity. If a patient may benefit from treatment with pomalidomide the investigator together with the principle investigator will discuss the possibility of further treatment including maintenance treatment with pomalidomide on a case-by-case decision. This additional treatment will be performed within the follow-up period of the study, data will be collected and duration will be maximally 12 cycles.
Treatment starts with pomalidomide as single agent therapy: 0.5 mg/day. Prednisolone will be started in the absence of PD as randomized either at start of cycle 4 or start of cycle 7 (starting dose: 30 mg/day for 28 days followed by 15 mg/day and 10 mg/day for 28 days), if no response acc. to IWG-MRT (no CR, PR, CI, TI) was achieved.
If PD: treatment is stopped. Otherwise, continuous treatment at least until end of cycle 12 is intended. For patients responding to the combination treatment (pomalidomide/prednisolone) a concom. treatment after cycle 6 or 9 (depending on the randomization result) with prednisolone in doses equal or below 7.5 mg/day are allowed.
If a patient may benefit from treatment with pomalidomide the invest. and the PI will discuss the possibility of further treatment including maintenance treatment with pomalidomide on a case-by-case decision (max. duration: 12 cycles).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00949364
|Aachen, Germany, 52074|
|Charité Universitätsmedizin Berlin|
|Berlin, Germany, 13353|
|Zentrum für Ambulante Hämatologie und Onkologie|
|Bonn, Germany, 53119|
|BAG Freiberg-Richter, Jacobasch, Wolf, Illmer (Gemeinschaftspraxis)|
|Dresden, Germany, 01307|
|Düsseldorf, Germany, 40225|
|Klinikum der Johann Goethe-Universität Frankfurt|
|Frankfurt, Germany, 60590|
|Freiburg, Germany, 79106|
|Universitätsklinikum Hamburg Eppendorf|
|Hamburg Eppendorf, Germany, 20246|
|Jena, Germany, 07740|
|Universitätsklinikum Magdeburg AöR|
|Magdeburg, Germany, 39120|
|Mannheim, Germany, 68167|
|Johannes Wesling Klinikum Minden|
|Minden, Germany, 32429|
|Stauferklinikum Schwäbisch Gmünd|
|Mutlangen, Germany, 73557|
|München, Germany, 80331|
|Ulm, Germany, 89081|