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

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ClinicalTrials.gov Identifier: NCT03773107
Recruitment Status : Recruiting
First Posted : December 12, 2018
Last Update Posted : July 2, 2019
Sponsor:
Collaborators:
Incyte Corporation
Multiple Myeloma Research Consortium
Amgen
Information provided by (Responsible Party):
Saad Z. Usmani, MD, Atrium Health

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Carfilzomib Drug: Ruxolitinib Drug: Dexamethasone Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Phase I
Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib
Drug: Carfilzomib
Irreversible proteasome inhibitor

Drug: Ruxolitinib
Oral JAK inihibtor

Drug: Dexamethasone
glucocorticoid

Phase II
Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen
Drug: Carfilzomib
Irreversible proteasome inhibitor

Drug: Ruxolitinib
Oral JAK inihibtor

Drug: Dexamethasone
glucocorticoid




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 4-month progression free survival ]
    In subjects who receive the combination treatment carfilzomib, dexamethasone and ruxolitinib.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 &#8805;75 ,000 cells/mm3 for subjects who have bone marrow plasmacytosis of <50%, or &#8805;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 &#8804;2 times the upper limit of the institutional normal values
    2. Total AST and ALT &#8804;3 times the upper limit of the institutional normal values
  5. Adequate renal function, as defined by the following: creatinine clearance (CrCl) &#8805;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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03773107


Contacts
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Contact: Kelly Bumgarner 704-403-2520 Kelly.Bumgarner@atriumhealth.org

Locations
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United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Kelly Bumgarner    704-403-2520    Kelly.Bumgarner@atriumhealth.org   
Sponsors and Collaborators
Saad Z. Usmani, MD
Incyte Corporation
Multiple Myeloma Research Consortium
Amgen
Investigators
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Principal Investigator: Saad Usmani, MD Atrium Health

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Responsible Party: Saad Z. Usmani, MD, Director of Clinical Research in Hematologic Malignancies, Director of Plasma Cell Disorder Program, Atrium Health
ClinicalTrials.gov Identifier: NCT03773107     History of Changes
Other Study ID Numbers: LCI-HEM-MYE-CRD-004
00031040 ( Other Identifier: CHS Internal )
First Posted: December 12, 2018    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents