Pomalidomide in Patients With Myeloproliferative Neoplasms in Fibrotic Stage

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Dr. Richard Schlenk, University of Ulm
ClinicalTrials.gov Identifier:
NCT00949364
First received: July 28, 2009
Last updated: September 9, 2013
Last verified: September 2013
  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.


Condition Intervention Phase
Myeloproliferative Neoplasms
Drug: Pomalidomide
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


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 Assigned Interventions
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 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

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).


  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   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:

  1. Age ≥50 years at the time of voluntarily signing an IRB/IEC-approved informed consent
  2. 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
  3. 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
  4. Splenomegaly (>11 cm diameter) and/or leukoerythroblastosis
  5. 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
  6. Subject must be willing to receive transfusion of blood products
  7. ECOG performance status < 3
  8. Female subjects with non-childbearing potential:

    • Agree to have a pregnancy test at baseline
  9. 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.
  10. 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.
    • 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.

Exclusion Criteria:

The presence of any of the following will exclude a patient from study enrollment:

  1. Females of childbearing potentials°, pregnant or breast feeding females
  2. BCR/ABL-positivity
  3. Diagnosis of ET (according to WHO 2008 criteria)
  4. Diagnosis of PV (according to WHO 2008 criteria)
  5. >20% blasts in peripheral blood or bone marrow
  6. Known positive status for HIV, HBV or HCV
  7. Prior treatment with IMiDs (thalidomide, lenalidomide) or with Interferon-alpha within a 3 month time period before screening
  8. History of thrombosis or pulmonary embolism
  9. Peripheral neuropathy >grade 1 CTC
  10. 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.
  11. 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
  12. Drug or alcohol abuse within the last 6 months
  13. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00949364

Locations
Germany
Universitätsklinikum Aachen
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
Universitätsklinikum Düsseldorf
Düsseldorf, Germany, 40225
Klinikum der Johann Goethe-Universität Frankfurt
Frankfurt, Germany, 60590
Universitätsklinikum Freiburg
Freiburg, Germany, 79106
Universitätsklinikum Hamburg Eppendorf
Hamburg Eppendorf, Germany, 20246
Universitätsklinikum Jena
Jena, Germany, 07740
Universitätsklinikum Magdeburg AöR
Magdeburg, Germany, 39120
Universitätsmedizin Mannheim
Mannheim, Germany, 68167
Johannes Wesling Klinikum Minden
Minden, Germany, 32429
Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany, 73557
Haematologisch-onkologische Praxis
München, Germany, 80331
Universitätsklinikum Ulm
Ulm, Germany, 89081
Sponsors and Collaborators
University of Ulm
  More Information

No publications provided

Responsible Party: Dr. Richard Schlenk, Prof.Dr., University of Ulm
ClinicalTrials.gov Identifier: NCT00949364     History of Changes
Other Study ID Numbers: MPN-SG 01-09
Study First Received: July 28, 2009
Last Updated: September 9, 2013
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 July 29, 2014