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Recurrent Plasma Cell MyelomaPhase 2NCT03256045

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

A Phase 2 study testing Carfilzomib, Chemosensitivity Assay and Dexamethasone in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by University of Washington at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carfilzomib, Chemosensitivity Assay and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
8 Feb 2018to 5 Feb 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: CLBH589DUS108T: Panobinostat With Carfilzomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Correlation With In Vitro Chemosensitivity Testing

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To correlate in vitro drug sensitivity testing with clinical response by determining the rate of in vitro drug sensitivity to panobinostat, carfilzomib, and dexamethasone singly and in combination, doublets and triplets.

SECONDARY OBJECTIVE:

  1. To monitor response rates (partial response [PR], very good partial response [VGPR], and complete response) using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.

EXPLORATORY OBJECTIVE:

  1. Progression free survival and overall survival will be assessed for up to 3 years after last dose.

OUTLINE:

Patients receive panobinostat orally (PO) on days 1, 3, 5, 15, 17, and 19. Patients also receive carfilzomib intravenously (IV) and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay.

After completion of study treatment, patients are followed up every 3 months for up to 3 years.

Being tested
Carfilzomib, Chemosensitivity Assay, Dexamethasone, Laboratory Biomarker Analysis, Panobinostat
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV

  • Chemosensitivity AssayOther

    Also called Chemosensitivity Testing

    Undergo in vitro chemosensitivity testing

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PanobinostatDrug

    Also called Faridak, Farydak, LBH589

    Given PO

Study groups in NCT03256045
Study groupRoleWhat they receive
Treatment-panobinostat, carfilzomib, dexamethasone,chemo assayExperimentalPatients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19. Patients also receive carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay.
Receives: Drug: Carfilzomib; Other: Chemosensitivity Assay; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Panobinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best Overall Response, by Subject

    Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.

    Measured: 14 months

  2. Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject

    Multiple myeloma cells are added to assay with panobinostat. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-9.

    Measured: At baseline

  3. Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject

    Multiple myeloma cells are added to assay with carfilzomib. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells.

    Measured: At baseline

  4. Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject

    Multiple myeloma cells are added to assay with dexamethasone. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-6.

    Measured: At baseline

  5. Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.

    Concentration of carfilzomib and panobinostat in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI<1 synergy; CI>1 antagonism.

    Measured: At baseline

  6. Synergy of Panobinostat and Dexamethasone in Combination, Per Subject

    Concentration of panobinostat and dexamethasone in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = ([D1] in the combination / [D1] alone) + ([D2] in the combination / [D2] alone). Key: CI = 1 no synergy; CI<1 synergy; CI>1 antagonism.

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2017
  2. Study start8 Feb 2018
  3. Primary completion5 Feb 2021
  4. Study completion5 Feb 2021

Why it stopped: Terminated due to loss of funding and former PI left the institution

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03256045
Sponsor's protocol ID
9757
Other IDs
NCI-2017-00453, 9757, P30CA015704, RG1016013
Status last verified
May 2022
First submitted
16 Aug 2017
Last updated
9 May 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Chemosensitivity Assay and Dexamethasone in people with Recurrent Plasma Cell Myeloma and Refractory Plasma Cell Myeloma, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best Overall Response, by Subject (time frame: 14 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03256045.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2022.

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