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Multiple Myeloma in RelapsePhase 1PanRVDNCT01965353

A Phase I Study Of Panobinostat/Lenalidomide/Bortezomib/Dex for Relapsed And Relapsed/Refractory Multiple Myeloma

A Phase 1 study testing Panobinostat, Dexamethasone and Lenalidomide in people with Multiple Myeloma in Relapse, run by Dana-Farber Cancer Institute at 4 sites in United States.

Completed

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

Official record
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Trial summary

This research study is evaluating an investigational drug called "panobinostat" (LBH589) in combination with the standard agents lenalidomide, bortezomib, and dexamethasone as a possible treatment for multiple myeloma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma in Relapse
What is being tested?
Panobinostat, Dexamethasone and Lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
4 sitesUnited States
Study dates
Oct 2013to Sep 2021
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

  • Patients must meet the following criteria on screening examination. All laboratory assessments should be performed within 21 days of initiation of protocol therapy unless otherwise specified.
  • Participants must have a previous diagnosis of Multiple Myeloma, according to International Myeloma Foundation 2003 Diagnostic Criteria
  • Patients must have relapsed or relapsed and refractory disease after receiving 2 or more lines of therapy.
  • Relapse is the occurrence of any of the following: 1) >25% increase in M-protein from the baseline levels; 2) reappearance of M-protein that had disappeared; or 3) definite increase in the size and number of lytic bone lesions recognized on radiographs (compression fractures per se do not constitute a relapse).
  • Subjects will be considered refractory to therapy, as defined by progression during treatment or within 60 days after the completion of salvage treatment. Subjects with primary refractory disease are excluded.
  • This includes: 1) non-responding, non-progressing; and 2) progressive; primary refractory, progressive disease where patients meet criteria for true progressive disease (Durie 2006).
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  • Participants must have measurable myeloma, defined as one or more of the following:
  • serum M-protein ≥ 0.5 g/dl,
  • urine M-protein ≥ 200 mg/24 h, and/or
  • serum FLC assay: involved FLC level ≥ 10 mg/dl with abnormal serum FLC ratio.
  • Age ≥ 18 years at the time of signing informed consent.
  • ECOG performance status <2 (Karnofsky >60%)
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mlU/mL 10 to14 days prior to therapy and repeated again within 24 hours of starting lenalidomide and must either commit to complete abstinence from heterosexual contact or begin TWO acceptable methods of birth control, one highly effective method and one additional effective (barrier) method, AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must practice complete abstinence or agree to use a condom during sexual contact with a FCBP even if they have had a successful vasectomy. All participants agree to enroll and comply with the RevAssist® program for the prevention of pregnancy.
  • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months
  • Ability to understand and the willingness to sign a written informed consent document. Voluntary written informed consent must be obtained before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Who cannot join

  • Participants who exhibit any of the following conditions at screening will not be eligible:
  • Participants with primary refractory disease
  • Participants who have a history of prior MM treatment with panobinostat, or an alternative HDAC-inhibitor.
  • Participant has ≥ Grade 2 peripheral neuropathy on clinical examination within 21 days before initiation of protocol therapy.
  • Renal insufficiency, defined as creatinine clearance < 60 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy. The Cockcroft-Gault formula should be used for calculating creatinine clearance values: 140-age) x Body mass (kg) x 0.85 (female) or 1.0 (male)/serum creat. (mg/dL) x 72
  • Platelet count <75,000cells/mm3at time of screening evaluation. Transfusion may not be used to meet platelet eligibility criteria within 7 days of obtaining screening evaluation.
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  • Participants with an absolute neutrophil count (ANC) < 1500 cells/mm3 at time of screening evaluation. Growth factor may not be used to meet ANC eligibility criteria within 7 days of obtaining screening evaluation.
  • Participants with hemoglobin level < 8.0 g/dL, at time of screening. Transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation.
  • Participants with hepatic impairment, defined as bilirubin > 1.5 x institutional upper limit of normal (ULN) or AST (SGOT), ALT (SGPT), or alkaline phosphatase > 2x institutional ULN, within 21 days of initiation of protocol therapy. Patients with benign hyperbilirubinemia (e.g., Gilbert's syndrome) are eligible
  • Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its equivalent) for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to study treatment.)
  • Concomitant use of drugs that may cause a prolongation of the QTcF or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • Concomitant use of CYP3A4 inhibitors at time of screening. If use of CYP3A4 inhibitors becomes medically necessary during study, they must be used with caution.
  • Anti-myeloma therapy, including radiotherapy, within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) prior to Day 1 and who have not recovered from side effects (to ≤ Grade 1) of those therapies.
  • Known significant cardiac abnormalities, including:
  • History or presence of sustained ventricular tachyarrhythmia. (Participants with a history of atrial arrhythmia are eligible but should be discussed with the investigator prior to enrollment).
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as HR < 50 bpm. Participants with pacemakers are eligible if HR ≥ 50 bpm
  • QTcF interval ≥ 450 milliseconds on screening ECG;
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Participants with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug.
  • Other clinically significant heart disease (e.g. CHF NY Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Serious, intercurrent illness including, but not limited to, clinically relevant active infection, known active hepatitis B or C viral infection, known HIV infection, uncontrolled diabetes mellitus, or serious co-morbid medical conditions such as chronic restrictive pulmonary disease, and cirrhosis.
  • Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study.
  • Prior malignancy (within the last 5 years) except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
  • Known hypersensitivity to acyclovir or similar anti-viral drug
  • POEMS syndrome or AL Amyloidoses
  • Known intolerance to steroid therapy
  • Participants who have had prior allogeneic stem cell transplantation with evidence of active graft-versus-host disease requiring immunosuppressive therapy
  • Participants receiving any other investigational agents.
  • Participants with known brain metastases.
  • Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to lenalidomide, bortezomib, panobinostat and/or dexamethasone.
  • Female participants pregnant or breast-feeding.
  • Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat.
  • Participants with diarrhea > CTCAE grade 2
  • Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of the surgery.
  • Participants 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: A Phase I Open Label Study Of Panobinostat In Combination With Lenalidomide, Bortezomib, And Dexamethasone In Patients With Relapsed And Relapsed/Refractory Multiple Myeloma

This research study is evaluating an investigational drug called "panobinostat" (LBH589) in combination with the standard agents lenalidomide, bortezomib, and dexamethasone as a possible treatment for multiple myeloma.

Read the detailed description

In this research study, the participant will be given a study drug-dosing diary for each treatment cycle. Each treatment cycle lasts 21 days (3 weeks) . The diary will also include special instructions for taking the study drug(s).

The investigator are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants that have multiple myeloma, not everyone who participates in this research study will receive the same dose of the study drug. The dose each participant will get will depend on the number of participants who have been enrolled in the study before each participant and how well they have tolerated their doses.

Each treatment cycle will be 21 days long. The participant will have to come to the clinic on days 1, 4, 5, 8, 10 and 11 in Cycle 1 and on days 1, 4, 8 and 11 in Cycles 2 and beyond. Days 1 and 5 of Cycle 1 will take about 8 hours. Every other visit should take about 1-4 hours, however there is always the possibility that it could take longer.

Study Drugs:

  • Panobinostat is a capsule that the participant will take three times a week for the first two the weeks of each cycle. Then participant will have one week off study medication.
  • Bortezomib will be administered in clinic as a subcutaneous injection twice a week during the first two weeks of each 21 day cycle.
  • Lenalidomide will be taken orally once daily on days 1-14 of each cycle.
  • Dexamethasone will be taken orally on the days of and after bortezomib administration during Cycles 1-8, and on days 1, 8 and 15 for Cycles 9 and beyond.

Planned Follow-up: The investigators would like to monitor the participant's medical condition even after the participants are no longer participating in the study. The investigators would like to do this by calling the participants on the telephone once every 6 months to see how the participant is doing. Keeping in touch with the participant and checking on their condition helps the investigator look at the long-term effects of the research study.

Being tested
Panobinostat, Dexamethasone, Lenalidomide, Bortezomib
Keywords
Relapsed Multiple Myeloma, Relapse-Refractory 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

    • Panobinostat - single oral dose on days 1, 3, 5, 8, 10 and 12 and followed by a 9-day rest period.

  • DexamethasoneDrug

    Dexamethasone - oral dose on Days 1, 2, 4, 5, 8, 9, 11 and 12 followed by a 9-day rest period

  • LenalidomideDrug

    Also called Revlimid

    Lenalidomide - daily oral dose on Days 1-14 followed by 7-day rest period

  • BortezomibDrug

    Also called Velcade

    Bortezomib - subcutaneous injection, on Days 1, 4, 8, and 11 followed by a 10-day rest period. At least 72 hours should elapse between bortezomib doses, but if needed an interval of 70 hours is permitted

Study groups in NCT01965353
Study groupRoleWhat they receive
PanobinostatExperimentalPanobinostat - single oral dose on days 1, 3, 5, 8, 10 and 12 and followed by a 9-day rest period. * Bortezomib - subcutaneous injection twice a week during the first two weeks of each 21 day cycle. * Dexamethasone oral dose on the days of and after bortezomib administration during Cycles 1-8, and on days 1, 8 and 15 for Cycles 9 and beyond. * Lenalidomide - oral dose once daily on days 1-14 of each cycle. Accrual to the next higher dose level will not occur until the safety and tolerability of the prior dose level(s) has been determined at the end of the first cycle. Each cycle of treatment will consist of 21 days. Accrual to the next higher dose level will not occur until the safety and tolerability of the prior dose level(s) has been determined at the end of the first cycle
Receives: Drug: Panobinostat; Drug: Dexamethasone; Drug: Lenalidomide; Drug: Bortezomib

What is being measured

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

  1. MTD (Maximum Tolerated Dose) of panobinostat in combination with RVD

    Measured: 2 Years

  2. Recommended dose of the combination for Phase 2 studies in participants with relapsed and relapsed/refractory multiple myeloma (MM) with SC bortezomib.

    Measured: 2 Years

Secondary outcomes (3)

  1. Response to pan-RVD (minimal response or better

    Measured: 2 Years

  2. Progression-free survival (PFS)

    Measured: 2 Years

  3. Duration of response

    Measured: 2 Years

Timeline

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

  1. First posted18 Oct 2013 (estimated)
  2. Study startOct 2013
  3. Primary completionMar 2019
  4. Study completionSep 2021

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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01965353
Sponsor's protocol ID
13-262
Acronym
PanRVD
Status last verified
Sep 2021
First submitted
10 Oct 2013
Last updated
5 Sep 2021
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Panobinostat, Dexamethasone and Lenalidomide in people with Multiple Myeloma in Relapse, run by Dana-Farber Cancer Institute at 4 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 15 inclusion and 36 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 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

MTD (Maximum Tolerated Dose) of panobinostat in combination with RVD (time frame: 2 Years). The study lists 2 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 NCT01965353.

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 5 Sep 2021.

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