Clinical Trials /

A Clinical Study to Test the Effects of Ruxolitinib And Thalidomide Combination for Patients With Myelofibrosis

NCT03069326

Description:

The purpose of this study is to test any good and bad effects of the study drugs called ruxolitinib and thalidomide. Ruxolitinib and thalidomide could shrink the cancer, but it could also cause side effects.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Study to Test the Effects of Ruxolitinib And Thalidomide Combination for Patients With Myelofibrosis
  • Official Title: Evaluation of Ruxolitinib And Thalidomide Combination as a Therapy for Patients With Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: 16-1498
  • NCT ID: NCT03069326

Conditions

  • Myelofibrosis

Interventions

DrugSynonymsArms
RuxolitinibRuxolitinib and Thalidomide
ThalidomideRuxolitinib and Thalidomide

Purpose

The purpose of this study is to test any good and bad effects of the study drugs called ruxolitinib and thalidomide. Ruxolitinib and thalidomide could shrink the cancer, but it could also cause side effects.

Trial Arms

NameTypeDescriptionInterventions
Ruxolitinib and ThalidomideExperimentalAfter 3 cycles of ruxolitinib treatment, either prior to study enrollment or through the ruxolitinib run-in phase, patients who meet eligibility criteria will be treated with ruxolitinib and thalidomide orally on days 1-28 of a 28 day cycle. Cycles will be continued until the patient wishes to be removed from the study, unacceptable toxicity develops, disease progression, treating physician recommends removal, or termination of study occurs.
  • Ruxolitinib
  • Thalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of myelofibrosis (either primary or post essential
             thrombocythemia/polycythemia vera) requiring therapy, including those previously
             treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2
             or high risk according to International Working Group (IWG) criteria.

          -  Patients taking ruxolitinib at the time of enrollment must have been taking
             ruxolitinib for a minimum of 3 months, and must have been on a stable dose of
             ruxolitinib for a minimum of 4 weeks immediately prior to enrollment.

          -  Patients taking ruxolitinib at the time of enrollment must be deemed to have had a
             suboptimal response (less than partial response per IWG criteria) to ruxolitinib
             single-agent therapy or deemed to have progression of disease (per IWG criteria).

          -  Age ≥ 18 years at the time of signing the informed consent.

          -  ECOG performance status 0 to 2.

          -  Patients must have adequate organ function as demonstrated by the following:

               1. Direct bilirubin < 2.0 mg/dL, unless due to Gilbert's disease

               2. Serum creatinine < 2.0 mg/dL.

               3. ALT and AST ≤ 3 x upper limit of normal (unless the transaminitis is considered
                  to be related to MF

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 14 days prior to and
             again within 24 hours* of starting thalidomide and must either commit to continued
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control, one highly effective method and one additional effective method AT THE SAME
             TIME, at least 4 weeks before she starts taking thalidomide. FCBP must also agree to
             ongoing pregnancy testing. Men must agree to use a condom during sexual contact with
             a female of child bearing potential even if they have had a successful vasectomy. All
             patients must be counseled at a minimum of every 28 days about pregnancy precautions
             and risks of fetal exposure.

          -  All study participants must be registered into the mandatory REMS® program, and be
             willing and able to comply with the requirements of REMS®

          -  Platelets ≥ 50000/uL and ANC ≥ 1000

          -  All study participants must be able to swallow oral medication

        Exclusion Criteria:

          -  Use of any other standard anti-neoplastic drug or growth factor (e.g., anagrelide,
             G-CSF, revlimid, clofarabine) except hydroxyurea or experimental drugs, with the
             exception of Ruxolitinib, less than 14 days or 5-half lives prior to starting study
             therapy and/or lack of recovery from all toxicity from previous therapy to grade 1 or
             better.

          -  Known prior clinically relevant hypersensitivity reaction to thalidomide, including
             the development of erythema nodosum if characterized by a desquamating rash.

          -  Prior therapy with thalidomide in combination with ruxolitinib

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form, which places the
             subject at unacceptable risk if he/she were to participate in the study or which
             confounds the ability to interpret data from the study.

          -  Lactating females.

          -  Known positive for HIV or hepatitis B or C per institutional standard of care

          -  Participants with prior history of thromboembolic disease (i.e. deep venous
             thrombosis (DVT) or pulmonary embolism (PE) within the last six months, as
             thalidomide has demonstrated an increased risk of DVT or PE

          -  Known to have a hypercoagulability syndrome (e.g.: antithrombin III, deficiency,
             anticardiolipin syndrome etc).

          -  Concurrent use of strong inducers or strong inhibitors of CYP3A4 (strong inducers are
             rifampin and St. John's Wort, carbamazepine, phenytoin, and barbiturates such as
             phenobarbital; strong inhibitors are HIV-antivirals, clarithromycin, itraconazole,
             ketoconazole, nefadozone and telithromycin).

          -  Concurrent use of strong inducers or strong inhibitors of CYP3A4 (strong inducers are
             rifampin and St. John's Wort, carbamazepine, phenytoin, and barbiturates such as
             phenobarbital; strong inhibitors are HIV-antivirals, clarithromycin, itraconazole,
             ketoconazole, nefadozone and telithromycin).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:best objective response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:(ORR; complete response, partial response, and clinical improvement by IWG-MRT) in the first six cycles of the combination therapy. Clinical improvement for this endpoint will be defined as the change in anemia, spleen, and symptom response from the time of the initiation the combination therapy. The ORR will be defined as the best response by the completion of cycle 6 of combination therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Ruxolitinib
  • Thalidomide
  • 16-1498

Last Updated

April 19, 2017