Clinical Trials /

Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary MF

NCT01644110

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.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary MF
  • Official Title: A Phase-Ib/II Study of Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: POMINC(MPNSG02-12)
  • SECONDARY ID: 2012-002431-29
  • NCT ID: NCT01644110

Conditions

  • Primary Myelofibrosis
  • Secondary Myelofibrosis
  • PMF
  • SMF
  • Post-PV MF
  • Post-ET MF

Interventions

DrugSynonymsArms
INCB018424/CC-4047ruxolitinib/pomalidomide

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.

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".
    

Trial Arms

NameTypeDescriptionInterventions
ruxolitinib/pomalidomideExperimentalruxolitinib treatment will be started at 10 mg twice daily, whereas the dose of pomalidomide will be 0.5 mg once daily.
  • INCB018424/CC-4047

Eligibility 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. Patient treatment with Ruxolitinib within a 14 days time period before Screening-phase

         13. History of thrombosis or pulmonary embolism within 6 months prior to study entry

         14. Peripheral neuropathy >grade 1 CTC

         15. 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.

         16. 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

         17. Drug or alcohol abuse within the last 6 months

         18. Patients with other malignancy either in the medical history or currently active other
             than non-melanoma skin cancers.

         19. 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.

         20. Patients receiving any medication listed in the Appendix V "Prohibited Medications"
             (within 7 days prior to the first dose of study drug).

         21. 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.

         22. Patients under ongoing treatment with another investigational medication or having
             been treated with an investigational medication within 28 days of screening.

         23. No consent for biobanking.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall safety profile of ruxolitinib and pomalidomide combination observed during treatment, as well as cumulative incidence of leukemic transformation
Time Frame:one year
Safety Issue:
Description: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
Measure:Progression-free survival
Time Frame:three years
Safety Issue:
Description:
Measure:duration of response
Time Frame:three years
Safety Issue:
Description:
Measure:overall survival
Time Frame:three years
Safety Issue:
Description:
Measure:Quality of life
Time Frame:three years
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Ulm

Last Updated

December 10, 2014