Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
72

Inclusion Criteria

Age ≥18 years at the time of voluntarily signing an IRB/IEC-approved informed consent
Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia*
Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.**
...
Age ≥18 years at the time of voluntarily signing an IRB/IEC-approved informed consent
Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia*
Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.**
understand that the investigational product could have a potential teratogenic risk.
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*
agree not to share study medication with another person and to return all unused study drug to the investigator.
agree to abstain from donating blood while taking investigational product.
Diagnosis of Myeloproliferative Neoplasms (MPN) either de novo myelofibrosis according to current WHO criteria (PMF), secondary myelofibrosis (post-PV MF and post-ET MF) according to the IWG-MRT consensus terminology) (Appendix I)
Splenomegaly (>11 cm total diameter) and/or leukoerythroblastosis
ECOG performance status <3
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
Reliable contraception should be maintained throughout the study and for 28 days after study treatment discontinuation*
be counseled about pregnancy precautions and risks of fetal exposure.
Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods*
Subject must be willing to receive transfusion of blood products

Exclusion Criteria

Patient treatment with Ruxolitinib within a 14 days time period before Screening-phase
History of malignancy except for i) adequately treated local basal cell or squamous cell carcinoma of the skin, ii) asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, or iii) any other cancer that has been in complete remission for ≥ 5 years
Known positive status for HIV, HBV or HCV
...
Patient treatment with Ruxolitinib within a 14 days time period before Screening-phase
History of malignancy except for i) adequately treated local basal cell or squamous cell carcinoma of the skin, ii) asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, or iii) any other cancer that has been in complete remission for ≥ 5 years
Known positive status for HIV, HBV or HCV
History of thrombosis or pulmonary embolism within 6 months prior to study entry
thrombocytopenia <100 /nl or transfusion-dependent thrombocytopenia
Patients eligible for hematopoietic stem cell transplantation (suitable candidate and suitable donor is available)
>20% blasts in peripheral blood or bone marrow
Prior treatment with IMiDs (thalidomide, lenalidomide, pomalidomide) or with Interferon-alpha within a 3 month time period before Screening-phase
Diagnosis of ET (according to WHO 2016 criteria)
Patients with response to standard therapy as recommended by the Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO/Onkopedia)
BCR/ABL-positivity
Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 28 days of screening.
Patients receiving any medication listed in the Appendix V "Prohibited Medications" (within 7 days prior to the first dose of study drug).
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.
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
No consent for biobanking.
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.
Diagnosis of PV (according to WHO 2016 criteria)
Drug or alcohol abuse within the last 6 months
Peripheral neuropathy >grade 1 CTC
Pregnant or breast feeding females
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.
neutropenia <0.5 /nl

Summary

Conditions
  • PMF
  • Post ET MF
  • Post PV MF
  • Primary Myelofibrosis
  • Secondary Myelofibrosis
  • SMF
Type
Interventional
Phase
Phase 1 & Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Intervention Model Description: Cohort 1 (Patient 1 - Patient 41): ruxolitinib treatment will be started at 10 mg twice daily up to 25 mg twice daily, whereas the dose of pomalidomide will be 0.5 mg once daily. Cohort 2 (Patient 42 - Patient 90): ruxolitinib treatment will be started at 10 mg twice daily up to 25 mg twice daily, whereas the dose of pomalidomide will be started at 0.5 mg once daily up to 2 mg once daily.Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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 twic...

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".

Inclusion Criteria

Age ≥18 years at the time of voluntarily signing an IRB/IEC-approved informed consent
Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia*
Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.**
...
Age ≥18 years at the time of voluntarily signing an IRB/IEC-approved informed consent
Anemia with hemoglobin level of <10 g/dl or transfusion-dependent anemia*
Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.**
understand that the investigational product could have a potential teratogenic risk.
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*
agree not to share study medication with another person and to return all unused study drug to the investigator.
agree to abstain from donating blood while taking investigational product.
Diagnosis of Myeloproliferative Neoplasms (MPN) either de novo myelofibrosis according to current WHO criteria (PMF), secondary myelofibrosis (post-PV MF and post-ET MF) according to the IWG-MRT consensus terminology) (Appendix I)
Splenomegaly (>11 cm total diameter) and/or leukoerythroblastosis
ECOG performance status <3
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
Reliable contraception should be maintained throughout the study and for 28 days after study treatment discontinuation*
be counseled about pregnancy precautions and risks of fetal exposure.
Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods*
Subject must be willing to receive transfusion of blood products

Exclusion Criteria

Patient treatment with Ruxolitinib within a 14 days time period before Screening-phase
History of malignancy except for i) adequately treated local basal cell or squamous cell carcinoma of the skin, ii) asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, or iii) any other cancer that has been in complete remission for ≥ 5 years
Known positive status for HIV, HBV or HCV
...
Patient treatment with Ruxolitinib within a 14 days time period before Screening-phase
History of malignancy except for i) adequately treated local basal cell or squamous cell carcinoma of the skin, ii) asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, or iii) any other cancer that has been in complete remission for ≥ 5 years
Known positive status for HIV, HBV or HCV
History of thrombosis or pulmonary embolism within 6 months prior to study entry
thrombocytopenia <100 /nl or transfusion-dependent thrombocytopenia
Patients eligible for hematopoietic stem cell transplantation (suitable candidate and suitable donor is available)
>20% blasts in peripheral blood or bone marrow
Prior treatment with IMiDs (thalidomide, lenalidomide, pomalidomide) or with Interferon-alpha within a 3 month time period before Screening-phase
Diagnosis of ET (according to WHO 2016 criteria)
Patients with response to standard therapy as recommended by the Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO/Onkopedia)
BCR/ABL-positivity
Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 28 days of screening.
Patients receiving any medication listed in the Appendix V "Prohibited Medications" (within 7 days prior to the first dose of study drug).
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.
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
No consent for biobanking.
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.
Diagnosis of PV (according to WHO 2016 criteria)
Drug or alcohol abuse within the last 6 months
Peripheral neuropathy >grade 1 CTC
Pregnant or breast feeding females
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.
neutropenia <0.5 /nl

Locations

Jena, 07740
Hamburg, 20246
Minden, 32429
Aachen, 52074
Dresden, 01307
...
Jena, 07740
Hamburg, 20246
Minden, 32429
Aachen, 52074
Dresden, 01307
Magdeburg, 39120
Tübingen, 72076
Mainz, 55131
Köln, 50937
Bad Saarow, 15526
Mutlangen, 73557
Ulm, 89081
Augsburg, 86150
Mannheim, 68167
Essen, 45147
Düsseldorf, 40225
Freiburg, 79106

Tracking Information

NCT #
NCT01644110
Collaborators
Not Provided
Investigators
  • Principal Investigator: Konstanz Doehner, MD University of Ulm
  • Konstanz Doehner, MD University of Ulm