Monoclonal Antibody-Based Sequential Therapy for Deep Remission in Multiple Myeloma (MASTER)

Overview

This trial will assess the safety and efficacy of an induction therapy using the combination of dexamethasone, lenalidomide (revlimid), daratumumab (Darzalex) and carfilzomib (Kyprolis) to treat patients with newly diagnosed multiple myeloma. The therapy with KRdD (Kyprolis, Revlimid, dexamethasone, Darzalex) will be followed by autologous hematopoietic cell transplantation (auto-HCT) and KRdD consolidation. The hypothesis is that the KRdD therapy particularly in combination with the auto-HCT will be safe and lead to deep remission. The trial will also assess the monitoring for minimal residual disease (MRD) resurgence to determine if continuous therapy is needed or discontinuation of therapy.

The study has four cycles (28-days each) of drug therapy prior to being evaluated for auto-HCT. After the completion of induction therapy, the patient will be evaluated for a transplant of their own hematopoietic stem cells. If, after the transplant, the patient still has detectable multiple myeloma, the patient will proceed to a series of consolidation blocks, up to three, consisting of four cycles of the KRdD at specified dosages and time frames. After completion of consolidation therapy, maintenance therapy will begin until disease progression or intolerance.

SparkCures ID 941
Trial Phase Phase 2
Enrollment 82 Patients
Treatments
Trial Sponsors
  • University of Alabama at Birmingham
Trial Collaborators
  • Amgen
  • Janssen Research & Development
NCT Identifier

NCT03224507

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Age >18 years with no upper age limit
  • Diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • No prior MM-directed therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m2) and/or cyclophosphamide up to 1000 mg/m2 administered for management of acute manifestations of MM (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment. If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment must be available.
  • Measurable disease meeting at least one of the following criteria:

    1. Serum monoclonal (M) protein ≥1.0 g/dl
    2. ≥ 200 mg of M protein/24h in the urine
    3. Serum-free light chain ≥10 mg/dL and abnormal kappa to lambda ratio.
  • Life expectancy ≥12 months.
  • Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 μmol/L) within 21 days prior to initiation of therapy.
  • Creatinine clearance (CrCl) ≥ 40 mL/minute within 21 days prior to start of therapy either measured or calculated using a standard formula (eg. Cockcroft and Gault).
  • Written informed consent in accordance with federal, local, and institutional guidelines.
  • Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception. Male subjects must agree to practice contraception.
  • All subjects must agree to comply with and be enrolled in Revlimid REMS program.

Exclusion Criteria:

  • Diagnosis of amyloidosis, Crow-Fukase syndrome, Waldenstrom's macroglobulinemia, smoldering MM.
  • Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.
  • Known FEV1 or cDLCO < 50% of predicted.
  • Pregnant or lactating females.
  • Known human immunodeficiency virus infection.
  • Active hepatitis B (Hepatitis B core antibody positive and subsequent Hepatitis B surface antigen positive or Hepatitis B DNA positive) or C infection (Hepatitis C antibody positive and subsequent detectable viral load).
  • Unstable angina or myocardial infarction within 4 months prior to registration, New York Heart Association Class II, III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker.
  • Cerebrovascular disease manifested as prior stroke at any time or TIA in the 12 months prior to initiation of therapy
  • Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or localized thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas.
  • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 21 days prior to registration.
  • Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
  • Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 21 days prior to registration.
  • Contraindication or intolerance to required supportive care medications (Aspirin and Acyclovir).
  • Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Not Currently Accepting Patients

The following is a listing of trial locations that are not currently open and accepting patients.

Alabama
North Carolina
Ohio
Oregon
Tennessee
Wisconsin
Verified Medical College of Wisconsin - Froedtert Hospital

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