Overview

Panobinostat, Carfilzomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Status:
Terminated
Trial end date:
2021-02-05
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies how well panobinostat, carfilzomib, and dexamethasone work in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as carfilzomib and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Using multiple myeloma cells from patients' blood samples, the researchers will do laboratory tests to look at how well each of the drugs, alone and in different combinations, kill multiple myeloma cells. If the laboratory tests work well, they may be used in the future to help plan treatment for future patients.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Washington
Collaborators:
National Cancer Institute (NCI)
SecuraBio
Treatments:
BB 1101
Dexamethasone
Dexamethasone acetate
Ichthammol
Panobinostat
Criteria
Inclusion Criteria:

- Diagnosis of multiple myeloma refractory to or relapsed after >= 1 line of prior
therapy (International Myeloma Working Group [IMWG] criteria)

- Measurable disease, as indicated by one of the following:

- Serum monoclonal (M)-protein >= 1.0 g/dL

- Elevated involved free light chain >= 10 mg/dL as per IMWG criteria, and abnormal
ratio

- Urine Bence Jones protein > 200 mg/24 hour (hr)

- Absolute neutrophil count (ANC) >= 750/uL

- Platelet count >= 75,000/uL

- Hemoglobin >= 7 g/dL

- Creatinine =< 2.0 mg/dL or calculated creatinine clearance >= 30 mL/min

- Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is thought to be
due to Gilbert's syndrome

- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2.5 x
ULN

- Patients must avoid consumption of grapefruit, pomegranates, starfruit, Seville
oranges or products containing the juice of each during the entire study and
preferably 7 days before the first dose of study medications; orange juice is allowed

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, should have a pregnancy test prior to the initiation of treatment
and use highly effective methods of contraception during and for 3 months post study
treatment; highly effective contraception methods include total abstinence, female
sterilization, male sterilization, use of oral, injected, or implanted hormonal
methods of contraception or placement of an intrauterine device (IUD) or intrauterine
system (IUS) or other forms of hormonal contraception that have comparable efficacy;
women using hormonal contraceptives should additionally use a barrier method of
contraception; women are considered post-menopausal and not of child-bearing potential
if they have had 12 months of natural amenorrhea or have had surgical bilateral
oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at
least 6 weeks ago

- Sexually active males must use a condom during intercourse while taking study drug and
for 6 months after stopping treatment; males should not father a child in this period;
a condom is required to be used also by vasectomized men as well as during intercourse
with a male partner; female partners of sexually active men should also use an
effective contraception during treatment and for 6 months after their male partner has
stopped taking the drug

Exclusion Criteria:

- Another bone marrow malignancy

- Another cancer with expected survival of < 2 years

- Active viral, bacterial, or fungal infection progressing on current treatment

- Clinically significant uncontrolled heart disease and/or recent cardiac event within 6
months prior to enrollment, such as:

- History of angina pectoris, symptomatic pericarditis, or myocardial infarction

- Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiogram
(ECHO) or multi gated acquisition (MUGA) scan

- History or presence of any significant, uncontrolled, or persistent cardiac
arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias or conduction
abnormality; stable atrial fibrillation within 6 months prior to randomization is
permitted

- Presence of unstable atrial fibrillation (ventricular response rate > 100 beats
per minute [bpm]); NOTE: patients with stable atrial fibrillation can be enrolled
provided they do not meet other cardiac exclusion criteria

- Resting heart rate < 50 bpm

- Complete left bundle branch block (LBBB), bifascicular block

- Congenital long QT syndrome

- Any clinically significant ST segment and/or T-wave abnormalities

- Corrected QT (QTcF) > 450 msec for males and > 470 msec for females using
Fridericia's correction on screening electrocardiogram (ECG)

- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)

- Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 150 mmHg
and/or diastolic blood pressure (DBP) >= 100 mmHg with or without
antihypertensive medication; NOTE: initiation or adjustment of antihypertensive
medication(s) is allowed prior to screening

- Other clinically significant heart disease or vascular disease

- Currently taking medications that have known or definite risk of prolonging the QT
interval or inducing Torsades de pointes (TdP); the medication must be discontinued or
switched to a safe alternative medication prior to starting treatment; specific
exception is allowed for patients on long-standing medications that have risk of
prolonging QT interval or inducing TdP if screening ECG does not indicate a prolonged
QT abnormality

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of panobinostat or dexamethasone (e.g. ulcerative disease
uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or
small bowel resection)

- Unresolved diarrhea >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2
or a medical condition associated with chronic diarrhea (such as irritable bowel
syndrome, inflammatory bowel disease)

- Major surgery =< 14 days prior to starting study treatment or side effects of surgery
that have not recovered to < CTCAE grade 2