Clinical Trials /

LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma

NCT03773107

Description:

The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment carfilzomib, dexamethasone, and ruxolitinib.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma
  • Official Title: LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Phase I/II Study of Carfilzomib, Ruxolitinib, and Low Dose Dexamethasome for Carfilzomib-Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: LCI-HEM-MYE-CRD-004
  • SECONDARY ID: 00031040
  • NCT ID: NCT03773107

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
CarfilzomibPhase I
RuxolitinibPhase I
DexamethasonePhase I

Purpose

The primary objective of Phase I is to establish the maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and dexamethasone. The primary objective of phase II is to evaluate progression-free survival (PFS) at 4 months in multiple myeloma subjects who receive the combination treatment carfilzomib, dexamethasone, and ruxolitinib.

Detailed Description

      This is an open-label, Phase I/II study of carfilzomib, ruxolitinib, and low-dose
      dexamethasone for carfilzomib-refractory multiple myeloma. Phase I is designed to evaluate
      overall maximum tolerated dose (MTD) of ruxolitinib in combination with carfilzomib and
      dexamethasone in the following cohorts: Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg
      ruxolitinib, Cohort 3) 15mg ruxolitinib. Phase II is designed to evaluate 4-month
      progression-free survival (PFS) in the following cohorts: Cohort A) non-responders to Phase I
      regimen, Cohort B) responders to Phase I regimen. Up to 18 evaluable subjects will be
      enrolled in Phase I over approximately 12 months. An additional 30 evaluable subjects will be
      enrolled in Phase II over 24 months.
    

Trial Arms

NameTypeDescriptionInterventions
Phase IExperimentalCohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib
  • Carfilzomib
  • Ruxolitinib
  • Dexamethasone
Phase IIOtherCohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen
  • Carfilzomib
  • Ruxolitinib
  • Dexamethasone

Eligibility Criteria

        Subjects must meet all of the following criteria:

          1. Documented history of relapsed and/or refractory multiple myeloma with > 2 lines of
             therapy. One of the prior lines of therapy must have been a carfilzomib containing
             regimen with evidence of relapse or progression within the last 60 days of the
             carfilzomib containing regimen with a carfilzomib dose of at least 27 mg/m2.
             Carfilzomib containing regimen at the standard dose of 20/27 mg/m2 is acceptable.

          2. Measurable disease, as defined by at least one of the following:

               1. Serum monoclonal protein level ≥0.5 g/dL for IgG, IgA, or IgM disease

               2. Urinary M-protein excretion of ≥200 mg over a 24-hour period

               3. Involved free light chain level ≥10 mg/dL, along with an abnormal free light
                  chain ratio

          3. Adequate bone marrow reserves, as defined by the following:

               1. Absolute neutrophil count (ANC) ≥1000 cells/mm3 within 1 week of the initiation
                  of treatment

               2. Platelet count of ≥75 ,000 cells/mm3 for subjects who have bone marrow
                  plasmacytosis of <50%, or ≥50,000 cells/mm3 for subjects who have bone marrow
                  plasmacytosis of >50%

          4. Adequate hepatic function, as defined by the following:

               1. Total bilirubin ≤ 2 times the upper limit of the institutional normal values

               2. Total AST and ALT ≤ 3 times the upper limit of the institutional normal values

          5. Adequate renal function, as defined by the following: creatinine clearance (CrCl) ≥ 30
             mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and
             Gault formula.

          6. Adequate cardiac function defined as LVEF ≥ 40% by MUGA, echocardiogram or cardiac
             MRI.

          7. Be 18-75 years of age

          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          9. FOCBP and male subjects who are sexually active with FOCBP must agree to use two
             highly effective (as determined per the Investigator) methods of contraception during
             the study and for 30 days (female subjects) or for 90 days (male subjects) following
             the last dose of study treatment including a male condom.

         10. Ability to understand and the willingness to sign a written informed consent document.

        Subjects must not meet any of the following criteria:

          1. Non-secretory multiple myeloma

          2. Known amyloidosis

          3. Known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly,
             endocrinopathy, monoclonal protein, and skin changes)

          4. Clinically significant illness including, but not limited to the following: active
             systemic infection, uncontrolled hypertension (as defined by BP > 160/90), New York
             Heart Association Class III and IV heart failure, unstable angina pectoris, myocardial
             infarction within the past 6 months of consent, uncontrolled cardiac arrhythmia, or
             any other condition (including laboratory abnormalities) that, in the opinion of the
             Investigator, places the subject at unacceptable risk for adverse outcome if he/she
             were to participate in the study

          5. Prior cerebrovascular accident with persistent neurologic deficit.

          6. Psychiatric illness/social situations that would limit compliance with study treatment
             and requirements

          7. Pregnant or breast feeding. Females of childbearing potential (FOCBP) must have a
             negative serum pregnancy test within the 7 days prior to study drug administration and
             a negative urine pregnancy test within the 3 days prior to the first study drug
             administration.

          8. Known human immunodeficiency virus (HIV) infection

          9. Active hepatitis B and/or hepatitis C infection

         10. Currently active second malignancy, other than non-melanoma skin cancer and carcinoma
             in situ of the cervix, should not be enrolled. Subjects are not considered to have a
             currently active malignancy if they have completed therapy for a prior malignancy, are
             disease free from prior malignancies for >5 years, and are considered by their
             physician to be at less than 30% risk of relapse. In addition, subjects with basal
             cell carcinoma of the skin, superficial carcinoma of the bladder, carcinoma of the
             prostate with a current PSA value of <0.5 ng/mL, or cervical intraepithelial neoplasia
             will be eligible. Finally, subjects who are on hormonal therapy for a history of
             either prostate cancer or breast cancer may enroll, provided that there has been no
             evidence of disease progression during the previous three years.

         11. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
             carfilzomib).

         12. Contraindication to any of the required concomitant drugs or supportive treatments or
             intolerance to hydration due to preexisting pulmonary or cardiac impairment including
             pleural effusion requiring thoracentesis or ascites requiring paracentesis.

         13. Known intolerance to carfilzomib.

         14. Co-administration with strong CYP3A4 inhibitors (such as, but not limited to,
             boceprevir, clarithromycin, indinavir, itraconazole, ketoconazole,
             lopinavir/ritonavir, ritonavir, mibefradil, nefazodone, nelfinavir, posaconazole,
             saquinavir, telaprevir, telithromycin, voriconazole) as well as fluconazole (a dual
             inhibitor of CYP3A4 and CYP2C9).
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:4-month progression free survival
Safety Issue:
Description:In subjects who receive the combination treatment carfilzomib, dexamethasone and ruxolitinib.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Saad Z. Usmani, MD

Last Updated

December 12, 2019