Beta test our new site. Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage

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1 1 von :18 Beta test our new site. Home Search Study Topics Glossary Study 1 of 1 for search of: NCT Previous Study Return to Search Results Next Study Full Text View Tabular View No Study Results Posted Related Studies Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage This study is currently recruiting participants. Verified July 2012 by University of Ulm First Received on July 28, Last Updated on July 16, 2012 History of Changes Sponsor: Information provided by (Responsible Party): ClinicalTrials.gov Identifier: University of Ulm Dr. Richard Schlenk, University of Ulm NCT Purpose 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.

2 2 von :18 Condition Intervention Phase Myeloproliferative Neoplasms Drug: Pomalidomide Phase 2 Study Type: Study Design: Official Title: Interventional Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment Multi-Center Phase II Study With Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage Resource links provided by NLM: MedlinePlus related topics: Cancer U.S. FDA Resources Further study details as provided by University of Ulm: Primary Outcome Measures: 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 ] Secondary Outcome Measures: 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 ] Estimated Enrollment: 95 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) Arms Experimental: Pomalidomide 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 Assigned Interventions Drug: Pomalidomide 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

3 3 von :18 additional treatment will be performed within the follow-up period of the study, data will be collected and duration will be maximally 12 cycles. (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). Eligibility Ages Eligible for Study: Genders Eligible for Study: Accepts Healthy Volunteers: 50 Years and older Both No Criteria Inclusion Criteria: Both female and male patients meeting the mentioned inclusion and exclusion criteria will be included in this clinical trial. The risk to get PMF or SMF does not depend on a patient's gender. Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study: 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: All Subjects: Exclusion Criteria: 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. 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. Agree not to share study medication with another person and to return all unused study drug to the investigator No more than a 12-weeks-supply of study drug will be dispensed at a time. The presence of any of the following will exclude a patient from study enrollment: 1. Females of childbearing potentials, pregnant or brea st feeding females

4 4 von :18 2. BCR/ABL-positivity Diagnosis of ET (according to WHO 2008 criteria) Diagnosis of PV (according to WHO 2008 criteria) >20% blasts in peripheral blood or bone marrow Known positive status for HIV, HBV or HCV Prior treatment with IMiDs (thalidomide, lenalidomide) or with Interferon-alpha within a 3 month time period before screening History of thrombosis or pulmonary embolism Peripheral neuropathy >grade 1 CTC No consent for registration, storage and processing of the individual disease-characteristics and course as well as information of the family physician about study participation. Presence of any medical/psychiatric condition or laboratory abnormalities which may limit full compliance with the study, increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study Drug or alcohol abuse within the last 6 months Patients with a "currently active" second malignancy other than nonmelanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year. Criteria for women of non-childbearing potential: A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria: Age 50 years and naturally amenorrhoeic for 1 year. Amenorrhoea following cancer therapy does not rule out childbearing potential Premature ovarian failure confirmed by a specialist gynecologist Previous bilateral salpingo-oophorectomy, or hysterectomy XY genotype, Turner syndrome, uterine agenesis Contacts and Locations Please refer to this study by its ClinicalTrials.gov identifier: NCT Contacts Contact: Richard F Schlenk, MD richard.schlenk@uniklinik-ulm.de Contact: Frank Stegelmann, MD frank.stegelmann@uniklinik-ulm.de Locations Germany Universitätsklinikum Aachen Aachen, Germany, Contact: Jost Edgar, MD Principal Investigator: Edgar Jost, MD Helios Klinikum Bad Saarow Bad Saarow, Germany, Contact: Ulrich Bitz, MD ulrich.bitz@helios-kliniken.de Sub-Investigator: Ulrich Bitz, MD Charité Universitätsmedizin Berlin Berlin, Germany, Principal Investigator: Igor Wolfgang Blau, MD Zentrum für Ambulante Hämatologie und Onkologie Bonn, Germany, Contact: Walter Verbeek, MD wverbeek@zaho-rheinland.de Not yet recruiting

5 5 von :18 Principal Investigator: Walter Verbeek, MD BAG Freiberg-Richter, Jacobasch, Wolf, Illmer (Gemeinschaftspraxis) Dresden, Germany, Contact: Thomas Illmer illmer@onkologie-dresden.net Principal Investigator: Thomas Illmer, PD Dr. med Universitätsklinikum Düsseldorf Düsseldorf, Germany, Contact: Norbert Gattermann, MD gattermann@med.uni-duesseldorf.de Principal Investigator: Andrea Kündgen, MD Klinikum der Johann Goethe-Universität Frankfurt Frankfurt, Germany, Contact: Oliver Ottmann ottmann@em.uni-frankfurt.de Principal Investigator: Oliver Gerhard Ottmann, MD Universitätsklinikum Freiburg Freiburg, Germany, Contact: Cornelius F Waller, MD Principal Investigator: Cornelius F Waller, MD Universitätsklinikum Hamburg Eppendorf Hamburg Eppendorf, Germany, Contact: Philippe Schafhausen, MD schafhausen@uke.de Principal Investigator: Philippe Schafhausen, MD Universitätsklinikum Jena Jena, Germany, Contact: Andreas Hochhaus, MD Principal Investigator: Andreas Hochhaus, Md Universitätsklinikum Magdeburg AöR Magdeburg, Germany, Contact: Florian Heidel, MD florian.heidel@med.ovgu.de Principal Investigator: Daniel Lipka, MD Universitätsmedizin Mannheim Mannheim, Germany, Contact: Andreas Reiter andreas.reiter@umm.de Principal Investigator: Andreas Reiter, MD Johannes Wesling Klinikum Minden Minden, Germany, Contact: Martin Griesshammer, MD Principal Investigator: Martin Griesshammer, MD Stauferklinikum Schwäbisch Gmünd Mutlangen, Germany, Principal Investigator: Holger Hebart, MD Haematologisch-onkologische Praxis München, Germany, Contact: Petro E Petrides, Prof. Dr. petro.petrides@t-online.de; petrides@onkologiemuenchen.de Principal Investigator: Petro E Petrides, Prof. Dr. med. Universitätsklinikum Ulm Ulm, Germany, Contact: Richard F Schlenk, MD Contact: Frank Stegelmann, MD Sponsors and Collaborators University of Ulm richard.schlenk@uniklinik-ulm.de frank.stegelmann@uniklinik-ulm.de More Information No publications provided Responsible Party: Dr. Richard Schlenk, Prof.Dr., University of Ulm ClinicalTrials.gov Identifier: NCT History of Changes Other Study ID Numbers: MPN-SG 01-09

6 6 von :18 Study First Received: July 28, 2009 Last Updated: July 16, 2012 Health Authority: Germany: Federal Institute for Drugs and Medical Devices Keywords provided by University of Ulm: Myeloproliferative Neoplasms Pomalidomide Fibrotic Stage Patients with Myeloproliferative Neoplasms in Fibrotic Stage Additional relevant MeSH terms: Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Thalidomide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents ClinicalTrials.gov processed this record on August 12, 2012 Contact Help Desk Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine, U.S. National Institutes of Health, U.S. Department of Health & Human Services, USA.gov, Copyright, Privacy, Accessibility, Freedom of Information Act