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



Status:Recruiting
Conditions:Blood Cancer, Hematology, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:3/28/2019
Start Date:March 14, 2018
End Date:April 1, 2023
Contact:Luciano J Costa, MD, PhD
Email:ljcosta@uabmc.edu
Phone:205-934-9695

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

Multiple myeloma (MM), a plasma cell disorder, is the second most common hematologic
malignancy in the U.S. No standard curative therapy has yet been found. A variety of
therapeutic measures including high dose melphalan, induction therapy, and continuous therapy
have been used but the goal of complete response without relapse has not been achieved. More
active treatment regimens and better tools for response assessment are needed.

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. Duration of therapy will be guided by
eradication of minimal residual disease (MRD). The hypothesis is that the KRdD therapy
particularly in combination with the auto-HCT will be safe and lead to deep remission.
Patients who become MRD- will discontinue therapy (no maintenance therapy) and be actively
monitored for resurgence of MRD or clinical relapse.

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.
We found this trial at
4
sites
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Eva Medvedova, MD
Phone: 503-494-1453
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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1720 2nd Ave S
Birmingham, Alabama 35233
(205) 934-4011 
Phone: 205-934-6709
University of Alabama at Birmingham The University of Alabama at Birmingham (UAB) traces its roots...
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Birmingham, AL
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750 Highland Avenue
Madison, Wisconsin 53792
Principal Investigator: Natalie Callander
Phone: 608-406-2034
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Madison, WI
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2220 Pierce Ave
Nashville, Tennessee 37232
615-936-8422
Principal Investigator: Robert F Cornell, MD
Phone: 615-343-7190
Vanderbilt-Ingram Cancer Center The Vanderbilt-Ingram Cancer Center, located in Nashville, Tenn., brings together the clinical...
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Nashville, TN
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