Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary MF (POMINC)

This study is currently recruiting participants.
Verified August 2013 by University of Ulm
Sponsor:
Information provided by (Responsible Party):
Konstanze Doehner, University of Ulm
ClinicalTrials.gov Identifier:
NCT01644110
First received: July 16, 2012
Last updated: August 7, 2013
Last verified: August 2013
  Purpose

The proposed study is an open-label, single-arm, Phase-Ib/II trial to assess the efficacy of oral drug combination ruxolitinib and pomalidomide in primary and secondary MF patients.


Condition Intervention Phase
Primary Myelofibrosis
Secondary Myelofibrosis
PMF
SMF
Post-PV MF
Post-ET MF
Drug: INCB018424/CC-4047
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase-Ib/II Study of Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary Myelofibrosis

Resource links provided by NLM:


Further study details as provided by University of Ulm:

Primary Outcome Measures:
  • Best response rate within 12 treatment cycles according to the IWG-MRT criteria (including CR, PR, CI) and red cell transfusion (RCT) independency according to Gale et al 2010 and 2011). [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall safety profile of ruxolitinib and pomalidomide combination observed during treatment, as well as cumulative incidence of leukemic transformation [ Time Frame: one year ] [ Designated as safety issue: No ]
    Overall safety profile of ruxolitinib and pomalidomide combination characterized by type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of adverse events (AEs) and laboratory abnormalities observed during treatment, as well as cumulative incidence of leukemic transformation

  • Progression-free survival [ Time Frame: three years ] [ Designated as safety issue: No ]
  • duration of response [ Time Frame: three years ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: three years ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: three years ] [ Designated as safety issue: No ]
    Quality of life assessed by the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF Protocol 5/25/11), change in ECOG performance status from study entry to each visit where the variable is measured.


Estimated Enrollment: 72
Study Start Date: August 2013
Estimated Study Completion Date: January 2021
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ruxolitinib/pomalidomide
ruxolitinib treatment will be started at 10 mg twice daily, whereas the dose of pomalidomide will be 0.5 mg once daily.
Drug: INCB018424/CC-4047
For all patients the starting dose of ruxolitinib in this trial is 10mg twice daily po; pomalidomide will be administered at a permanent dose of 0.5 mg po once daily.

Detailed Description:

The proposed study is an open-label, single-arm, Phase-Ib/II trial to assess the efficacy of oral drug combination ruxolitinib and pomalidomide in primary and secondary MF patients. Dosages of the drugs are derived from previous Phase-I/II studies; ruxolitinib treatment will be started at 10 mg twice daily, whereas the dose of pomalidomide will be 0.5 mg once daily.

Dose reductions and discontinuations will be allowed in case of myelosuppressive effects.

Intra-patient dose escalation will be permitted for ruxolitinib to optimize efficacy of the therapeutic regimen; pomalidomide will be given in a permanent dosage of 0.5mg per day.

Treatment response will be evaluated continuously after each treatment cycle (1 cycle = 28 days) according to the IWG-MRT criteria expanded by the response criterion RCT-independency.

In case of progressive disease study therapy will be stopped; In patients showing response or stable disease, continuous therapy within the study is intended for a maximum of 12 treatment cycles; After completion of 12 treatment cycles, therapy can be continued if a measurable benefit of treatment is evident. This extension has to be discussed between the local and the principle investigator. Conditions leading to patient withdrawal from the study are detailed in the protocol "PATIENT WITHDRAWAL FROM STUDY PARTICIPATION".

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 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), secondary myelofibrosis (post-PV MF and post-ET MF) according to the IWG-MRT consensus terminology) (Appendix I)
  3. Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia*
  4. Splenomegaly (>11 cm total 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. Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.**
  9. Reliable contraception should be maintained throughout the study and for 28 days after study treatment discontinuation*
  10. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods*
  11. Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP. Males must agree not to donate semen or sperm*
  12. All subjects must:

    • understand that the investigational product could have a potential teratogenic risk.
    • be counseled about pregnancy precautions and risks of fetal exposure.
    • agree to abstain from donating blood while taking investigational product.
    • agree not to share study medication with another person and to return all unused study drug to the investigator.

Exclusion Criteria:

  1. Patients eligible for hematopoietic stem cell transplantation (suitable candidate and suitable donor is available)
  2. Patients with response to standard therapy as recommended by the Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO/Onkopedia)
  3. Pregnant or breast feeding females
  4. BCR/ABL-positivity
  5. Diagnosis of ET (according to WHO 2008 criteria)
  6. Diagnosis of PV (according to WHO 2008 criteria)
  7. >20% blasts in peripheral blood or bone marrow
  8. thrombocytopenia <100 /nl or transfusion-dependent thrombocytopenia
  9. neutropenia <0.5 /nl
  10. Known positive status for HIV, HBV or HCV
  11. Prior treatment with IMiDs (thalidomide, lenalidomide, pomalidomide) or with Interferon-alpha within a 3 month time period before Screening-phase
  12. History of thrombosis or pulmonary embolism within 6 months prior to study entry
  13. Peripheral neuropathy >grade 1 CTC
  14. 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.
  15. 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
  16. Drug or alcohol abuse within the last 6 months
  17. Patients with other malignancy either in the medical history or currently active other than non-melanoma skin cancers.
  18. Patients undergoing treatment with hematopoietic growth factor receptor agonists (i.e., erythropoietin [Epo], granulocyte colony stimulating factor (GCSF [Neupogen; Neulasta], romiplostim, eltrombopag) within a 4 weeks period prior to screening-phase.
  19. Patients receiving any medication listed in the Appendix V "Prohibited Medications" (within 7 days prior to the first dose of study drug).
  20. Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
  21. Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 28 days of screening.
  22. No consent for biobanking.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01644110

Contacts
Contact: Konstanze Doehner, MD 0049731500 ext 45543 konstanze.doehner@uniklinik-ulm.de
Contact: Frank Stegelmann, MD 0049731500 ext 45731 frank.stegelmann@uniklinik-ulm.de

Locations
Germany
University of Ulm Recruiting
Ulm, Germany, 89081
Contact: Konstanze Doehner, MD       konstanze.doehner@uniklinik-ulm.de   
Principal Investigator: konstanze Doehner, Md         
Sponsors and Collaborators
University of Ulm
Investigators
Principal Investigator: Konstanz Doehner, MD University of Ulm
  More Information

No publications provided

Responsible Party: Konstanze Doehner, Prof. Dr. Konstanze Doehner, University of Ulm
ClinicalTrials.gov Identifier: NCT01644110     History of Changes
Other Study ID Numbers: POMINC(MPNSG02-12), 2012-002431-29
Study First Received: July 16, 2012
Last Updated: August 7, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Primary Myelofibrosis
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 April 16, 2014