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Multiple MyelomaPhase 1NCT01549431

Study of the Combination of Panobinostat & Carfilzomib in Patients With Relapsed &/or Refractory Multiple Myeloma

A Phase 1 study testing Panobinostat, Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Emory University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to find out what effects, good and/or bad, the combination of panobinostat and carfilzomib have on the patient's cancer. It will determine the side effects of different dose levels of panobinostat and carfilzomib and determine the best dose and schedule of the two drugs to recommend for… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Panobinostat, Carfilzomib and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
3 sitesUnited States
Study dates
Jan 2012to Apr 2017
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Male or female patients aged ≥ 18 years old
  • Diagnosis of multiple myeloma (MM) following at least one prior therapy; there is no maximum number or prior therapies
  • Patients must have relapsed/ refractory disease and be in need of therapy with evidence of measurable disease defined as at least one of the following:
  • Serum M protein ≥ 0.5 g/dl (≥ 5g/l)
  • Urine M protein ≥ 200 mg/24 hours
  • Serum free light chain (FLC) assay: Involved FLC assay ≥ 10 mg/dl (≥100 mg/l) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
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  • Measurable plasmacytoma (Prior biopsy is acceptable)
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Patients must meet the following laboratory criteria:
  • Absolute neutrophil count (ANC) ≥ 1.0 x 10⁹/L (growth factors cannot be used within 3 days of screening)
  • Hemoglobin ≥ 8 g/dl (PRBC transfusions cannot be used within 3 days of screening)
  • Platelets ≥ 75 x 10⁹/L (platelet transfusions cannot be used within 3 days of screening)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 x ULN
  • Serum potassium ≥ lower limit of normal (LLN)
  • Total serum calcium [corrected for serum albumin] or ionized calcium ≥ LLN. (treatment of hypercalcemia is allowed and subjects may enroll if hypercalcemia returns to normal with standard treatment)
  • Serum magnesium ≥ LLN
  • Serum phosphorus ≥ LLN
  • Creatinine clearance ≥ 30 ml/min (Cockcroft-Gault calculation)
  • Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
  • Baseline multigated acquisition scan (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional normal
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
  • Must be willing and able to undergo bone marrow aspirates per protocol (with or without bone marrow biopsy per institutional guidelines). The bone marrow aspirate/biopsy must be adequate to allow for comparison for the on-study efficacy assessments.
  • Females of childbearing potential (FCBP) - An FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.

Who cannot join

  • Prior histone deacetylase (HDAC), dichloroacetate (DAC), or valproic acid for the treatment of cancer
  • Prior treatment with carfilzomib
  • Daily requirement for corticosteroids > prednisone 10 mg/day or equivalent
  • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
  • History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Principal Investigator prior to enrollment)
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  • History of congenital long QT syndrome
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as heart rate (HR) < 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
  • ECG evidence of acute ischemia or grade 3 conduction system abnormalities (unless subject has a pacemaker)
  • Screening ECG with a corrected QT interval (QTc) > 450 msec
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
  • Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) (Patients with a history of atrial arrhythmias may be eligible if they are controlled and approved by the Lead Principal Investigator)
  • Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat. Inability to take oral medications, requirement for IV alimentation, active peptic ulcer disease or prior surgical procedures or bowel resection affecting absorption of oral medications.
  • Patients with diarrhea > Common Toxicity Criteria for Adverse Effects (CTCAE) grade 1 (increase of 4 stools per day over baseline mild increase in ostomy output compared to baseline)
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug [allow 72 hour washout period]
  • Concomitant use of cytochrome P450 3A4 (CYP3A4) inhibitors
  • Patients who have received either vaccine or antibody based therapy within ≤ 8 weeks; chemotherapy within ≤ 4 weeks, immunomodulatory drugs (IMiDs) within 2 weeks; or radiation therapy to > 30% of marrow-bearing bone within ≤ 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Peripheral blood stem cell transplant within 12 weeks of first dose of study treatment
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control
  • Male patients whose sexual partners are FCBP not using effective birth control
  • Patients with a prior malignancy with in the last 3 years (except for basal or squamous cell carcinoma, or in situ cancer or low risk prostate cancer after curative therapy or with > 90% remission at 5 years)
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
  • Significant neuropathy (≥ grade 3 or grade 2 with pain) within 14 days of initiation of therapy
  • Subjects with evidence of mucosal or internal bleeding, an active bleeding diathesis and or known platelet transfusion refractoriness
  • Patients with contraindications to any of the required concomitant drugs or supportive treatments, including hypersensitivity to anticoagulation and antiplatelet options, antiviral drugs, or tolerance to hydration due to pre-existing pulmonary of cardiac impairment
  • Patients with hypersensitivity to any of the components of the drug including allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib), including voriconazole, ziprasidone, aripiprazole and amiodarone
  • Ongoing graft-versus-host disease

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Emory University Winship Cancer Institute

    Atlanta, Georgia, 30322

  • University of Chicago

    Chicago, Illinois, 60637

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Phase I Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed and/or Refractory Multiple Myeloma

The purpose of this study is to find out what effects, good and/or bad, the combination of panobinostat and carfilzomib have on the patient's cancer. It will determine the side effects of different dose levels of panobinostat and carfilzomib and determine the best dose and schedule of the two drugs to recommend for future studies. The study will assess the effects of the drug on multiple myeloma. In addition, tests to study the way the drugs work will also be done.

The combination of the 2 drug classes have shown both pre-clinical (studies done in the lab) and clinical (studies done with people) effects against multiple myeloma. For this reason, these 2 drugs are being studied in combination to determine the side effects and anti-myeloma effects of the 2 drugs.

Read the detailed description

This is a multi-center, open-label, phase I study of panobinostat, carfilzomib in patients with relapsed/refractory multiple myeloma. Based on the preclinical data supporting the use of combined histone de-acetylase (HDAC) and proteasome inhibition, the incidence of single-agent panobinostat and carfilzomib anti-myeloma activity, and clinical data demonstrating safety and efficacy of panobinostat with a different proteasome inhibitor (bortezomib), this study will evaluate the combination of panobinostat and carfilzomib in patients with relapsed/refractory multiple myeloma in a phase I trial.

Being tested
Panobinostat, Carfilzomib, Dexamethasone
Keywords
Multiple Myeloma
Medical subject headings
Multiple Myeloma

What participants receive

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

  • PanobinostatDrug

    Also called LBH589

    Panobinostat will be supplied as 5-mg or 20-mg pink/opaque-colored, hard gelatin capsules. Panobinostat is administered orally three times per week.

    • Standard 3+3 design
    • 3 out of 4 weeks

  • CarfilzomibDrug

    Also called Kyprolis

    Carfilzomib in Cycle 1 will be initiated intravenously at 20 mg/m² on Days 1 and 2 and escalated to 27 mg/m² for Days 8, 9, 15, and 16 of Cycle 1 and for the duration of treatment.

    • Standard 3+3 design
    • Days 1/2, 8/9 and 15/16 every 4 weeks

  • DexamethasoneDrug

    Also called Decadron

    Dexamethasone (4 mg) must be given prior to each carfilzomib infusion during Cycle 1. Dexamethasone pre-dose should continue through Cycle 2 if fever is observed post-dose, Cycle 2 Day 1, or thereafter associated with the infusion of carfilzomib.

Study groups in NCT01549431
Study groupRoleWhat they receive
Combo of Panobinostat and CarfilzomibExperimentalA cycle of therapy is 4 weeks (28 days in duration). Carfilzomib (with dexamethasone during cycle 1) will be administered intravenously infusion on days 1, 2 and 8, 9 and 15, 16 of every 28 day cycle. Panobinostat is administered orally three times per week.
Receives: Drug: Panobinostat; Drug: Carfilzomib; Drug: Dexamethasone

What is being measured

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

  1. Maximum tolerated dose (MTD) of the combination of panobinostat and carfilzomib

    Measured: 28 day cycle

Timeline

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

  1. First posted9 Mar 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionFeb 2016
  4. Study completionApr 2017

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01549431
Sponsor's protocol ID
IRB00049368
Other IDs
WCI2011-11/MMRC036
Status last verified
Jan 2019
First submitted
7 Mar 2012
Last updated
16 Jan 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Kaufman JL, Mina R, Jakubowiak AJ, Zimmerman TL, Wolf JJ, Lewis C, Gleason C, Sharp C, Martin T, Heffner LT, Nooka AK, Harvey RD, Lonial S. Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study. Blood Cancer J. 2019 Jan 4;9(1):3. doi: 10.1038/s41408-018-0154-8.

    PubMed 30610196

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Panobinostat, Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Emory University at 3 sites 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 24 inclusion and 31 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: finished, as of the sponsor's last update on 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose (MTD) of the combination of panobinostat and carfilzomib (time frame: 28 day cycle). 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 NCT01549431, which also lists 1 linked publication.

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 16 Jan 2019.

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