AzTrials
AzTrials

Multiple MyelomaPhase 1/2NCT00743288

Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma

A Phase 1/2 study testing Melphalan and Panobinostat in people with Multiple Myeloma, run by Oncotherapeutics 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
Search all trials

Trial summary

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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
Conditions the study is for
Multiple Myeloma
What is being tested?
Melphalan and Panobinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
4 sitesUnited States
Study dates
Jul 2008to Dec 2012
Phase
Phase 1/2
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, based on the following criteria:
  • Major criteria
  • Plasmacytomas on tissue biopsy (1)
  • Bone marrow plasmacytosis (> 30% plasma cells) (2)
  • Monoclonal immunoglobulin (Ig) spike on serum electrophoresis, IgG > 3.5 g/dL or IgA > 2.0 g/dL, and kappa or lambda light chain excretion > 1 g/day on 24-hour urine protein electrophoresis (3)
  • Minor Criteria
Show all 31Show fewer
  • Bone marrow plasmacytosis (10-30% plasma cells) (a)
  • Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b)
  • Lytic bone lesions ©)
  • Normal IgM < 50 mg/dL, IgA < 100 mg/dL, or IgG < 600 mg/dL (d)
  • Meets any of the following sets of multiple myeloma diagnostic criteria:
  • Any two of the major criteria
  • Major criterion 1 plus minor criterion b, c, or d
  • Major criterion 3 plus minor criterion a or c
  • Minor criteria a, b, and c, OR a, b, and d
  • Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours, or evidence of lytic bone disease
  • Must have received ≥ 1 prior treatment regimen OR refractory to most recent chemotherapy
  • Relapsed following stabilization or response to standard first-line chemotherapy (e.g., vincristine, doxorubicin hydrochloride, and prednisone or melphalan and prednisone) or first-line high-dose chemotherapy
  • Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to most recent chemotherapy, whether or not containing systemic corticosteroids
  • Prior treatment with ≤ 4 days of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for myeloma is not considered a regimen
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Life expectancy > 3 months
  • Platelet count ≥ 75 x 10^9/L (≥ 50 x 10^9/L if bone marrow is extensively infiltrated)
  • Absolute neutrophil count ≥ 1.5 x 10^9/L (≥ 1.0 x 10^9/L if bone marrow is extensively infiltrated)
  • Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 times ULN
  • Creatinine clearance ≥ 30 mL/min; creatinine > 10 mL/min and < 30 mL/min due to significant myelomatous involvement of the kidneys allowed with medical director approval
  • Serum potassium ≥ lower limit of normal (LLN)
  • Serum magnesium ≥ LLN
  • Serum phosphorus ≥ LLN
  • Prior localized radiotherapy

Who cannot join

  • Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome)
  • Plasma cell leukemia
  • Pregnant or nursing females; fertile patients must use effective contraception
  • Peripheral neuropathy > grade 2
  • Impaired cardiac function or clinically significant cardiac disease (including congenital long QT syndrome, history or presence of sustained ventricular tachyarrhythmia; history of ventricular fibrillation or Torsade de Pointes; bradycardia, defined as heart rate (HR) < 50 beats per minute (bpm) [pacemaker allowed provided HR ≥ 50 bpm]; corrected QT interval > 450 msec on screening ECG; left ventricular ejection fraction below normal on screening ECHO or multigated acquisition (MUGA) scan; right bundle branch block with left anterior hemiblock (bifascicular block); myocardial infarction or unstable angina within the past 6 months; New York Heart Association class III-IV congestive heart failure; uncontrolled hypertension; history of labile hypertension; history of poor compliance with an antihypertensive regimen)
  • Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
Show all 16Show fewer
  • Prior malignancy within the past 5 years except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix
  • Other concurrent severe and/or uncontrolled medical or psychiatric conditions (e.g., uncontrolled diabetes or active or uncontrolled infection), including abnormal laboratory values that could cause unacceptable safety risks or compromise protocol compliance
  • Known positivity for HIV or hepatitis B or C
  • Severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL)
  • Significant history of non-compliance to medical regimens or unwillingness or inability to comply with instructions given by the study staff
  • Concurrent medication that risk prolonging the QT interval or inducing Torsades de Pointes
  • Prior panobinostat
  • Received chemotherapy, bortezomib, thalidomide, lenalidomide or arsenic trioxide within 3 wks of enrollment (with the exception of nitrosoureas within 6 wks of enrollment)
  • Received corticosteroids (>10 mg/day prednisone or equivalent) within three weeks before enrollment.
  • Received immunotherapy within < 8 weeks; antibody 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.

Trial locations and contacts

4 sites in 1 country.

United States4 sites
  • Comprehensive Blood and Cancer Center

    Bakersfield, California, 93309-0633

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • Rocky Mountain Cancer Centers - Denver Midtown

    Denver, Colorado, 80218

  • James R. Berenson MD, Incorporated

    West Hollywood, California, 90069

Other trials in United States

About this study

Official title: A Phase I/II Study of Oral Melphalan Combined With LBH589 for Patients With Relapsed or Refractory Multiple Myeloma (MM)

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving melphalan together with panobinostat may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of melphalan when given together with panobinostat in treating patients with recurrent multiple myeloma.

Read the detailed description

OBJECTIVES:

Primary

  • To establish the maximum tolerated dose (MTD) and determine the dose-limiting toxicities (DLT) of panobinostat in combination with melphalan in patients with relapsed or refractory multiple myeloma. (Phase I)
  • To determine the dose of this regimen to be used in the Phase II portion of the study. (Phase I)
  • To determine the efficacy as evidenced by the response rate (combined complete response, very good partial response, partial response, and minimal response) in patients treated with this regimen. (Phase II)

Secondary

  • To obtain preliminary evidence of efficacy of the combination of LBH589 and melphalan for patients with relapsed or refractory multiple myeloma. (Phase I)
  • To determine the safety and tolerability of this regimen in these patients. (Phase II)
  • To determine time to disease progression, time to response, and duration of response in patients treated with this regimen. (Phase II)
  • To determine progression-free survival and overall survival of patients treated with this regimen. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.

Patients receive oral panobinostat once daily on days 1, 3, 5, 8, 10, and 12 and oral melphalan once daily on days 1, 3 and 5. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Being tested
Melphalan, Panobinostat
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, 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.

  • MelphalanDrug

    Also called Phenylalanine mustard, Alkeran

    Same as above

  • PanobinostatDrug

    Also called LBH589

Study groups in NCT00743288
Study groupRoleWhat they receive
Melphalan and PanobinostatExperimentalSchedule A: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 of a 28-day cycle and melphalan PO at 0.05 mg/kg on days 1-5 of week 1. Toxicity led to the following changes in dose and schedule Schedule B1: 10mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule B2: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1-4 and 0.05 mg/kg melphalan POon days 1, 3 and 5 of week 1. Schedule C: 20mg/daily of LBH589 PO on days 1, 3 and 5 of weeks 1 and 2 and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1 Schedule D1: 15 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D2: 15 mg/daily LBH589 PO and 0.10 mg/kg melphalan PO on days 1, 3 and 5 of week 1. Schedule D3: 20 mg/daily LBH589 PO and 0.05 mg/kg melphalan PO on days 1, 3 and 5 of week 1.
Receives: Drug: Melphalan; Drug: Panobinostat

What is being measured

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

  1. Maximum Tolerated Dose (MTD)

    Phase 1: to determine the MTD of panobinostat (LBH589) in combination with melphalan to be used in the Phase 2 portion of the study

    Measured: 12 months

  2. MTD

    Phase 1: to determine MTD of melphalan in combination with panobinostat to be used in the Phase 2 portion of the study

    Measured: 12 months

  3. Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) [ORR= Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)]; CBR=ORR + Minimal Response (MR)] Following Treatment With Panobinostat and Melphalan

    Responses were evaluated according to criteria modified from those developed by Blade et al., 1998 The reference point for evaluating response improvement is the baseline. This baseline reference point is also valid when a patient has already achieved a response and transitions through into a better response grade.

    Measured: 24 months

Secondary outcomes (2)
  1. Duration of Response

    Measured: First evidence of PR or better (for overall response) and MR or better (for clinical benefit response) to start of disease progression or death

  2. Time to Progression

    Measured: Time from the start of treatment to progressive disease

Timeline

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

  1. First posted28 Aug 2008 (estimated)
  2. Study startJul 2008
  3. Primary completionNov 2012
  4. Study completionDec 2012

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00743288
Sponsor's protocol ID
CDR0000612441
Other IDs
ONCOTHER-CLBH589BUS15T, LBH
Status last verified
Apr 2014
First submitted
27 Aug 2008
Last updated
8 May 2014
Data monitoring committee
No

Publications

  • Berenson JR, Hilger JD, Yellin O, Boccia RV, Matous J, Dressler K, Ghazal HH, Jamshed S, Kingsley EC, Harb WA, Noga SJ, Nassir Y, Swift RA, Vescio R. A phase 1/2 study of oral panobinostat combined with melphalan for patients with relapsed or refractory multiple myeloma. Ann Hematol. 2014 Jan;93(1):89-98. doi: 10.1007/s00277-013-1910-2. Epub 2013 Oct 18.

    PubMed 24135804

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Melphalan and Panobinostat in people with Multiple Myeloma, run by Oncotherapeutics 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 31 inclusion and 16 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 8 May 2014. 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 combined 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.

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 25 Apr 2014). 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?

Maximum Tolerated Dose (MTD) (time frame: 12 months). The study lists 3 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 NCT00743288, 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 8 May 2014.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in