- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03773107
LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Study of CRD for Carfilzomib-Refractory Multiple Myeloma
April 11, 2024 updated by: Wake Forest University Health Sciences
LCI-HEM-MYE-CRD-004 (MMRC-073 CARJAK): Phase I/II Study of Carfilzomib, Ruxolitinib, and Low Dose Dexamethasone for Carfilzomib-Refractory Multiple Myeloma
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
12
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Michigan
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Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute
-
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Levine Cancer Institute
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria
Subjects must meet all of the following criteria:
- 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.
Measurable disease, as defined by at least one of the following:
- Serum monoclonal protein level ≥0.5 g/dL for IgG, IgA, or IgM disease
- Urinary M-protein excretion of ≥200 mg over a 24-hour period
- Involved free light chain level ≥10 mg/dL, along with an abnormal free light chain ratio
Adequate bone marrow reserves, as defined by the following:
- Absolute neutrophil count (ANC) ≥1000 cells/mm3 within 1 week of the initiation of treatment
- 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%
Adequate hepatic function, as defined by the following:
- Total bilirubin ≤ 2 times the upper limit of the institutional normal values
- Total AST and ALT ≤ 3 times the upper limit of the institutional normal values
- 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.
- Adequate cardiac function defined as LVEF ≥ 40% by MUGA, echocardiogram or cardiac MRI.
- Be 18-75 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- 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.
- Ability to understand and the willingness to sign a written informed consent document.
- Recovered from all reversible acute toxic effects of prior therapy (other than alopecia) to ≤ Grade 1 or baseline.
Exclusion Criteria
Subjects must not meet any of the following criteria:
- Non-secretory multiple myeloma
- Known amyloidosis
- Known POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- 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
- Prior cerebrovascular accident with persistent neurologic deficit.
- Psychiatric illness/social situations that would limit compliance with study treatment and requirements
- 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.
- Known human immunodeficiency virus (HIV) infection
- Active hepatitis B and/or hepatitis C infection
- 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.
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
- 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.
- Known intolerance to carfilzomib.
- 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).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Phase I
Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib
|
Irreversible proteasome inhibitor
Other Names:
Oral JAK inhibitor
Other Names:
glucocorticoid
|
Other: Phase II
Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen
|
Irreversible proteasome inhibitor
Other Names:
Oral JAK inhibitor
Other Names:
glucocorticoid
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Limiting Toxicity (DLT)
Time Frame: 28 days
|
DLTs will be determined for each subject as a binary variable indicating whether or not the subject experienced a DLT during Cycle 1
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: approx. 5 years
|
Overall survival is defined as the duration from initiation of ruxolitinib treatment to the date of death from any cause.
|
approx. 5 years
|
Time to Progression
Time Frame: approx. 5 years
|
Time to progression (TTP) is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death.
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approx. 5 years
|
Duration of Response
Time Frame: approx. 5 years
|
Duration of response will be defined as the time from first objective status assessment of response to the time of first documented disease progression or death.
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approx. 5 years
|
Objective Response Rate (ORR)
Time Frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Objective response will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of PR or better as per the IMWG criteria
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Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Clinical Benefit Rate
Time Frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Clinical benefit will be determined for each subject as a binary variable indicating whether or not the subject achieved a best overall response of minimal response (MR) or better as determined by the IMWG criteria
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Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Disease Control Rate
Time Frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Disease control will be determined for each subject as a binary variable indicating whether or not the subject achieved a disease response or stable disease for greater than or equal to 8 weeks
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Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Progression-free Survival (PFS)
Time Frame: approx. 5 years
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PFS is defined as the duration of time from the initiation of study treatment with ruxolitinib to first occurrence of either progressive disease or death without progressive disease.
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approx. 5 years
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Time to Best Response
Time Frame: Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
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Time to best response will be defined as the time from initiation of ruxolitinib treatment to the time of best objective status assessment of response.
|
Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Shebli Atrash, MD, Wake Forest University Health Sciences
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 3, 2019
Primary Completion (Actual)
November 7, 2022
Study Completion (Actual)
February 21, 2024
Study Registration Dates
First Submitted
December 10, 2018
First Submitted That Met QC Criteria
December 11, 2018
First Posted (Actual)
December 12, 2018
Study Record Updates
Last Update Posted (Estimated)
April 15, 2024
Last Update Submitted That Met QC Criteria
April 11, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
Other Study ID Numbers
- IRB00081612
- 00031040 (Other Identifier: Advarra IRB)
- LCI-HEM-MYE-CRD-004 (Other Identifier: Atrium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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