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

NCT03773107 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB0008161200031040LCI-HEM-MYE-CRD-004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Myeloma

Keywords

Plasma Cell Neoplasms; Blood Malignancy

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT)

  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 Outcomes (8)

• Objective Response Rate (ORR)

  Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

• Clinical Benefit Rate

  Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

• Disease Control Rate

  Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

• Progression-free Survival (PFS)

  approx. 5 years

• Time to Best Response

  Approximately 180 days after treatment start (disease assessment occurred after every 28-day cycle)

Study Arms (2)

Phase I

EXPERIMENTAL

Cohort 1) 5mg ruxolitinib, Cohort 2) 10mg ruxolitinib, Cohort 3) 15mg ruxolitinib

Drug: Carfilzomib; Drug: Ruxolitinib; Drug: Dexamethasone

Phase II

OTHER

Cohort A) non-responders to Phase I regimen, Cohort B) responders to Phase I regimen

Drug: Carfilzomib; Drug: Ruxolitinib; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Irreversible proteasome inhibitor

Also known as: Kyprolis

Phase I; Phase II

Ruxolitinib DRUG

Oral JAK inhibitor

Also known as: Jakafi

Phase I; Phase II

Dexamethasone DRUG

glucocorticoid

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Incyte Corporation: collaborator
• Multiple Myeloma Research Consortium: collaborator
• Amgen: collaborator

Study Sites (2)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

carfilzomib; ruxolitinib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

The Phase II part of the trial did not open to enrollment. The MTD was not identified in the Phase I part of the trial.

Results Point of Contact

• Title: Jim Symanowski, PhD
• Organization: Levine Cancer Institute

james.symanowski@atriumhealth.org

9804422371

Study Officials

• Shebli Atrash, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 12, 2018
• Study Start: January 3, 2019
• Primary Completion: November 7, 2022
• Study Completion: February 21, 2024
• Last Updated: January 13, 2025
• Results First Posted: April 5, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)