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

NCT01644110 | Completed Phase 1 DMC

• 2 other identifiers: POMINC(MPNSG02-12)2012-002431-29
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Best response rate within 12 treatment cycles according to the IWG-MRT

  one year

Secondary Outcomes (7)

• Overall safety profile of ruxolitinib and pomalidomide combination observed during treatment, as well as cumulative incidence of leukemic transformation

  one year

• Progression-free survival

  three years

• duration of response

  three years

• overall survival

  three years

• Quality of life assessed by the Myeloproliferative Neoplasm Symptom

  three years

Study Arms (1)

ruxolitinib/pomalidomide

EXPERIMENTAL

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.

Drug: INCB018424/CC-4047

Interventions

INCB018424/CC-4047 DRUG

Cohort 1: For patients (1-41) the starting dose of ruxolitinib in this trial is 10 mg twice daily po; pomalidomide will be administered at a permanent dose of 0.5 mg po once daily. Cohort 2: For patients (42-90) the starting dose of ruxolitinib in this trial is 10 mg twice daily po; the starting dose of pomalidomide is 0.5 mg po once daily.

ruxolitinib/pomalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of voluntarily signing an IRB/IEC-approved informed consent
• 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)
• Anemia with hemoglobin level of \<10 g/dl or transfusion-dependent anemia\*
• Splenomegaly (\>11 cm total diameter) and/or leukoerythroblastosis
• 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
• Subject must be willing to receive transfusion of blood products
• ECOG performance status \<3
• Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.\*\*
• Reliable contraception should be maintained throughout the study and for 28 days after study treatment discontinuation\*
• Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods\*
• 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\*
• 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.

You may not qualify if:

• Patients eligible for hematopoietic stem cell transplantation (suitable candidate and suitable donor is available)
• Patients with response to standard therapy as recommended by the Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie (DGHO/Onkopedia)
• Pregnant or breast feeding females
• BCR/ABL-positivity
• Diagnosis of ET (according to WHO 2016 criteria)
• Diagnosis of PV (according to WHO 2016 criteria)
• \>20% blasts in peripheral blood or bone marrow
• thrombocytopenia \<100 /nl or transfusion-dependent thrombocytopenia
• neutropenia \<0.5 /nl
• Known positive status for HIV, HBV or HCV
• Prior treatment with IMiDs (thalidomide, lenalidomide, pomalidomide) or with Interferon-alpha within a 3 month time period before Screening-phase
• Patient treatment with Ruxolitinib within a 14 days time period before Screening-phase
• History of thrombosis or pulmonary embolism within 6 months prior to study entry
• Peripheral neuropathy \>grade 1 CTC
• 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.

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (17)

Universitätsklinikum Aachen - Med. Klinik IV

Aachen, 52074, Germany

Location

Hämatologisch onkologische Praxis

Augsburg, 86150, Germany

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Klinik für Innere Medizin Uniklinik Köln

Cologne, 50937, Germany

Location

BAG Freiberg-Richter, Jacobasch, Wolf, Illmer

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Uniklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Universitätsklinikum Magdeburg AöR

Magdeburg, 39120, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

University of Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Konstanz Doehner, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Konstanze Doehner

Model Details: 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.

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: July 18, 2012
• Study Start: August 1, 2013
• Primary Completion: April 1, 2024
• Study Completion: April 27, 2024
• Last Updated: March 30, 2025

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (17)