Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage

NCT00949364 | Completed Phase 2

• 1 other identifier: MPN-SG 01-09
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Myeloproliferative Neoplasms

Keywords

Myeloproliferative Neoplasms; Pomalidomide; Fibrotic Stage; Patients with Myeloproliferative Neoplasms in Fibrotic Stage

Outcome Measures

Primary Outcomes (1)

• Objective disease response, as defined by the IWG-MRT criteria for response in MF patients extended by the criterion RBC-transfusion independence (TI)

  one year

Secondary Outcomes (4)

• Overall safety profile of pomalidomide characterized by type, frequency, severity, timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during treatment

  one year

• Event-free survival

  three years

• Relapse-free survival

  three years

• Overall survival

  three years

Study Arms (1)

Pomalidomide

EXPERIMENTAL

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.

Drug: Pomalidomide

Interventions

Pomalidomide DRUG

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).

Pomalidomide

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Age ≥50 years at the time of voluntarily signing an IRB/IEC-approved informed consent
• Diagnosis of Myeloproliferative Neoplasms (MPN) either de novo myelofibrosis according to WHO criteria (PMF) \[20\], secondary myelofibrosis (post-PV MF and post-ET MF according to the IWG-MRT consensus terminology) \[21\] or unclassifiable MPN with biopsy proven myelofibrosis
• Anemia with hemoglobin level of \<10 g/dl or transfusion-dependent anemia and/or thrombocytopenia \<50 /nl or transfusion-dependent thrombocytopenia and/or neutropenia \<1.0 /nl
• Splenomegaly (\>11 cm diameter) and/or leukoerythroblastosis
• Adequate organ function, i.e. ALT and/or AST \<3 x upper limit of normal (ULN), total bilirubin \<3 x ULN, and serum creatinine \<2 mg/dl
• Subject must be willing to receive transfusion of blood products
• ECOG performance status \< 3
• Female subjects with non-childbearing potential:
• Agree to have a pregnancy test at baseline
• Male subjects:
• Agree to use condoms throughout study drug therapy, during any dose interruption and for four weeks after cessation of study therapy if their partner is of childbearing potential and has no contraception.
• Agree not to donate semen during study drug therapy and for four weeks after end of study drug therapy.
• All Subjects:
• Will be counseled about potential teratogenic risks of the study medication.
• Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (15)

Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Zentrum für Ambulante Hämatologie und Onkologie

Bonn, 53119, Germany

Location

BAG Freiberg-Richter, Jacobasch, Wolf, Illmer (Gemeinschaftspraxis)

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Klinikum der Johann Goethe-Universität Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg Eppendorf, 20246, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Universitätsklinikum Magdeburg AöR

Magdeburg, 39120, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Haematologisch-onkologische Praxis

München, 80331, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Related Publications (1)

• Schlenk RF, Stegelmann F, Reiter A, Jost E, Gattermann N, Hebart H, Waller C, Hochhaus A, Platzbecker U, Schafhausen P, Blau IW, Verbeek W, Heidel FH, Werner M, Kreipe H, Teleanu V, Benner A, Dohner H, Griesshammer M, Dohner K. Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis. Leukemia. 2017 Apr;31(4):889-895. doi: 10.1038/leu.2016.299. Epub 2016 Oct 24.

  PMID: 27774990 RESULT

MeSH Terms

Conditions

Myeloproliferative Disorders

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.Dr.

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 30, 2009
• Study Start: December 1, 2009
• Primary Completion: December 14, 2016
• Study Completion: December 14, 2016
• Last Updated: September 25, 2017

Record last verified: 2017-09

Locations

DE (15)