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Multiple MyelomaPhase 2NCT01651039

Phase II, Single-Center, Oral Panobinostat in Combination With Lenalidomide and Dexamethasone in Multiple Myeloma (MM)

A Phase 2 study testing Panobinostat, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Ajai Chari at 1 site 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 clinical research study is to find out the effects of a drug called panobinostat (LBH589) when given to people like you with multiple myeloma in combination with the drugs lenalidomide and dexamethasone. The safety of this combination of drugs will also be studied. 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, Lenalidomide and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
Jul 2012to 21 Dec 2016
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

  • Patients must have a history of symptomatic multiple myeloma according to the International Myeloma Working Group criteria (IMWG, 2003), as defined as the following three criteria:
  • Clonal plasma cells >10% on bone marrow biopsy
  • A monoclonal protein (paraprotein) in either serum or urine(except in cases of non-secretory myeloma)
  • Evidence of end-organ damage felt related to the plasma cell disorder (related organ or tissue impairment, ROTI, commonly referred to by the acronym "CRAB"):
  • Hypercalcemia serum Ca ≥ 11.5 mg/dL or
  • Renal insufficiency attributable to myeloma. Serum creatinine > 2mg/dL
Show all 36Show fewer
  • Anemia: Normochromic, normocytic with a hemoglobin value > 2g/dL below the lower limit of normal or a hemoglobin <10 g/dL
  • Bone lesions (lytic lesions, severe osteopenia or pathologic fractures
  • Patients must have received at least one prior line of therapy. For example; One prior line of therapy may consist of all predetermined components of induction followed by autologous stem cell transplantation and maintenance.
  • Patient has relapsed or relapsed/refractory MM.
  • Relapsed is defined as the development of disease progression following the achievement of stable disease (SD) or better to the most recent anti-MM regimen.
  • Refractory is defined as experiencing less than a partial response (PR) to or progressive disease (PD) within 6 months after completion of the most recent anti-MM regimen.
  • Patients must currently have measureable disease, as defined as:
  • a. Serum M protein ≥ 1.0 g/dl (≥ 10 mg/l)
  • Urine M protein ≥ 200 mg/24h
  • Serum free light chain assay: involved FLC level ≥ 10mg/dl (≥ 100 mg/l) provided serum FLC ratio is abnormal
  • If no monoclonal protein is detected (non-secretory disease), then > 30% monoclonal bone marrow plasma cells.
  • Patients must be suitable (according to their local product information) for treatment or re-treatment with lenalidomide \& dexamethasone. Note: patients previously treated with lenalidomide \& dexamethasone are eligible to participate in the trial.
  • Male or female adults ≥ 18 years old
  • ECOG Performance Status ≤ 2
  • Life expectancy > 12 weeks
  • Patients must have the following laboratory values:
  • ANC ≥ 1.5 x 109/L for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or an ANC > 1.0 x 109/Lfor patients in whom > 50% of bone marrow nucleated cells are plasma cells.
  • Hemoglobin ≥ 9 g/dl
  • Platelets ≥ 75x 109/L for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or > 50 x 109/L for patients in whom > 50% of bone marrow nucleated cells are plasma cells.
  • Calculated CrCl ≥ 50 mL/min (MDRD Formula)
  • Hepatic:
  • AST and ALT ≤ 2.5 x ULN,
  • Serum bilirubin ≤ 1.5 x ULN
  • Electrolytes:
  • Serum potassium ≥ LLN,
  • Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN
  • Serum magnesium ≥ LLN
  • Serum phosphorus ≥ LLN
  • Normal thyroid function (TSH and free T4) (Clinically euthyroid patients are acceptable).
  • Able to sign informed consent and to comply with the protocol

Who cannot join

  • 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 Novartis prior to enrollment)
  • Any history of ventricular fibrillation or torsade de pointes
  • Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if resting HR ≥ 50 bpm.
  • Screening ECG with a QTc > 450 msec
Show all 27Show fewer
  • 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., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat
  • Patients with diarrhea > CTCAE grade 2
  • 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
  • Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
  • Patients who have received either immunotherapy within < 8 weeks; chemotherapy within < 4 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.
  • Subject has received a cumulative dose of corticosteroids more than the equivalent of ≥ 140 mg of prednisone within the 2-week period before Cycle 1 Day 1.
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 24hrs of receiving the first dose of study medication.
  • Male patients whose sexual partners are WOCBP not using effective birth control
  • Patients with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • 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.
  • Patients with a history of Deep Vein Thrombosis or thromboembolism within < 6 months prior to starting study treatment
  • Patients for whom prophylactic anticoagulation therapy (eg. 325mg aspirin PO daily or warfarin (Coumadin®) 1-2 mg/day, or any other coumarin-derivative anticoagulants) is not an option.
  • Patients who have received allogeneic stem cell transplantation < 12 months prior to entering the study
  • Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy.
  • All patients must agree to follow the requirements for lenalidomide counseling, pregnancy testing and birth control. For women of childbearing potential (WOCBP) this includes pregnancy testing prior to prescribing lenalidomide and to either commit to continued abstinence from heterosexual intercourse or begin acceptable methods of birth control for 28 days prior to prescribing lenalidomide, during therapy and for 28 days after the last dose of lenalidomide. WOCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a WOCBP even if they have had a successful vasectomy and must agree not to donate semen during study drug therapy and for a period of time after therapy. All patients must abstain from donating blood, agree not to share lenalidomide with others and be counseled about the risks of lenalidomide. See Appendix 2 requirements including the definition of WOCBP.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: A Phase II, Single-Center, Open-Label Study Of Oral Panobinostat (LBH589) When Administered In Combination With Lenalidomide And Weekly Dexamethasone In Patients With Multiple Myeloma

The purpose of this clinical research study is to find out the effects of a drug called panobinostat (LBH589) when given to people like you with multiple myeloma in combination with the drugs lenalidomide and dexamethasone. The safety of this combination of drugs will also be studied. Your physical state, changes in the state of your multiple myeloma, and laboratory findings taken while on-study will help us decide if panobinostat combined with dexamethasone and lenalidomide is safe and effective.

This goal of this study therefore is to determine the activity of the combination of panobinostat thrice weekly every other week, lenalidomide, and weekly dexamethasone in a similar group of subjects. The doses of lenalidomide and dexamethasone will be that which is approved by the FDA for multiple myeloma and you will take each drug at a specific frequency over a 4 week (28 day) period. This period is called a "study cycle".

Read the detailed description

The study drug, panobinostat, is made by Novartis Pharmaceuticals Corporation. Panobinostat has not yet been approved by the Food and Drug Administration (FDA) and thus is considered an experimental drug in this research study. Panobinostat is not available to you "on the market" (available for you to buy). It is only available in clinical trials for patients like you with your medical condition. Panobinostat is a drug that may slow down the growth of multiple myeloma or kill multiple myeloma cells by blocking certain enzymes (proteins produced by cells). Panobinostat has shown effects against cancers such as multiple myeloma in laboratory studies and in studies using animals; however, it is not known if this medicine will show the same activity in humans. As of 31st December 2009, a total of 1116 patients have already received treatment with panobinostat.

Unlike panobinostat, lenalidomide (Revlimid©) and dexamethasone are approved by the FDA and are already available for purchase on the US market. Clinical trials have shown that lenalidomide, especially taken with dexamethasone, produces positive clinical responses with manageable side effects when given to subjects with multiple myeloma.

In this study, subjects will take panobinostat capsules, lenalidomide, and dexamethasone all orally. The purpose of this combination is to interfere with the cancerous cells in multiple and different ways as each of these drugs acts differently on cancer cells. By combining the drugs and giving them at the same time, it might be possible to slow the progression of your disease, rather than if study drugs were given separately. Researchers have combined laboratory studies on animals with this drug combination and the combined effect has been shown to be worthwhile to justify clinical trials in humans.

Being tested
Panobinostat, Lenalidomide, Dexamethasone
Keywords
Panobinostat, Lenalidomide, Dexamethasone
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

    Each cycle is 28 days. Panobinostat will be given 20 mg: Days 1,3,5,15,17,19.

  • LenalidomideDrug

    Also called Revlimid

    Each cycle is 28 days. Lenalidomide will be given 25 mg: Days 1-21.

  • DexamethasoneDrug

    Each cycle is 28 days. Dexamethasone will be given for patients 75 years old and younger a dose of 40 mg on Days 1, 8 and 15. Dexamethasone will be given for patients older than 75 years old, 20 mg on Days 1, 8 and 15.

Study groups in NCT01651039
Study groupRoleWhat they receive
Panobinostat, Lenalidomide and DexamethasoneExperimentalAll patients will receive oral panobinostat, lenalidomide and dexamethasone as per protocol.
Receives: Drug: Panobinostat; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

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

  1. The Best Overall Response Rate (ORR)

    The primary endpoint will be the best overall response rate (ORR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: up to 4 years

  2. Overall Response Rate for Len Refractory Patients

    The primary endpoint will be the best overall response rate (ORR)

    Measured: up to 4 years

Secondary outcomes (6)

  1. Response Rates

    Response Rates evaluated using the International Uniform Response Criteria the International Myeloma Working Group (2003).

    CR-Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow VGPR-Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component <100 mg per 24 h PR-50% reduction of serum M-protein and reduction in 24-h urinary M-protein by 90% or to <200 mg per 24 h MR-≥ 25% but < 49% reduction of serum M protein and reduction in 24 hour urine M protein by 50 - 89%, which still exceeds 200 mg/24hrs. In addition; if present at baseline, 25-49% reduction in the size of soft tissue plasmacytomas also required No increase in size or number of lytic bone lesions.

    SD-Not meeting criteria for CR, VGPR, PR or progressive disease PD-Laboratory or Biochemical Relapse increase of 25% from baseline

    Measured: up to 4 years

  2. Response Rates for Len Refractory Patients

    Response Rates evaluated using the International Uniform Response Criteria the International Myeloma Working Group (2003).

    CR-Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow VGPR-Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90 or greater reduction in serum M-component plus urine M-component <100 mg per 24 h PR-50% reduction of serum M-protein and reduction in 24-h urinary M-protein by 90% or to <200 mg per 24 h MR-≥ 25% but < 49% reduction of serum M protein and reduction in 24 hour urine M protein by 50 - 89%, which still exceeds 200 mg/24hrs. In addition; if present at baseline, 25-49% reduction in the size of soft tissue plasmacytomas also required No increase in size or number of lytic bone lesions.

    SD-Not meeting criteria for CR, VGPR, PR or progressive disease PD-Laboratory or Biochemical Relapse increase of 25% from baseline

    Measured: up to 4 years

  3. Clinical Benefit Rate

    The number of response rates in participants that have achieved MR, PR, VGPR, CR

    Measured: up to 4 years

  4. Clinical Benefit Rate for Len Refractory Patients

    The number of response rates in Lens Refractory participants that have achieved MR, PR, VGPR, CR

    Measured: up to 4 years

  5. Disease Control Rate

    The number of response rates participants with SD, MR, PR, VGPR, or CR

    Measured: up to 4 years

  6. Disease Control Rate for Lens Refractory Rate

    The number of response rates in Len refractory participants with SD, MR, PR, VGPR, or CR

    Measured: up to 4 years

Timeline

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

  1. First posted26 Jul 2012 (estimated)
  2. Study startJul 2012
  3. Primary completion21 Dec 2016
  4. Study completion21 Dec 2016

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
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01651039
Sponsor's protocol ID
GCO 12-0469
Other IDs
CLBH589DUS85T
Status last verified
Mar 2018
First submitted
24 Jul 2012
Last updated
9 Apr 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panobinostat, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Ajai Chari 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 36 inclusion and 27 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 9 Apr 2018. 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 Apr 2018). 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?

The Best Overall Response Rate (ORR) (time frame: up to 4 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 NCT01651039.

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 Apr 2018.

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