Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005212

Trial Description

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Title

A Phase-Ib/II Study of Ruxolitinib and Pomalidomide Combination Therapy in Patients With Primary and Secondary Myelofibrosis

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Trial Acronym

POMINC

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URL of the Trial

[---]*

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

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".

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Organizational Data

  •   DRKS00005212
  •   2013/10/23
  •   2012/07/16
  •   yes
  •   [---]*
  •   [---]*
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Secondary IDs

  •   2012-002431-29 
  •   NCT01644110  (ClinicalTrials.gov)
  •   POMINC(MPNSG02-12)  (University of Ulm)
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Health Condition or Problem studied

  •   Primary Myelofibrosis
  •   Secondary Myelofibrosis
  •   PMF
  •   SMF
  •   Post-PV MF
  •   Post-ET MF
  •   D47.4 -  [generalization D47: Other neoplasms of uncertain or unknown behaviour of lymphoid, haematopoietic and related tissue]
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Interventions/Observational Groups

  •   Drug: INCB018424/CC-4047
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
  •   [---]*
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Primary Outcome

- 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

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Secondary Outcome

- Overall safety profile of ruxolitinib and pomalidomide combination observed during treatment, as well as cumulative incidence of leukemic transformation; time frame: one year; 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
- duration of response; time frame: three years
- overall survival; time frame: three years
- Quality of life; time frame: three years; 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.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
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Recruitment

  •   [---]*
  •   2013/08/31
  •   72
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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.

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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.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • University of Ulm
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    •   [---]*
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    • University of Ulm
    • Konstanz Doehner, MD 
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    •   [---]*
    •   [---]*
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    • Konstanze Doehner, MD 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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    •   [---]*
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Status

  •   Recruiting ongoing
  •   [---]*
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   79
  •   2013/10/20
* This entry means the parameter is not applicable or has not been set.