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Relapsed and Bortezomib Refractory Multiple MyelomaPhase 2MACS1271NCT01083602

Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma

A Phase 2 study testing panobinostat, bortezomib and dexamethasone in people with Relapsed and Bortezomib Refractory Multiple Myeloma and Refractory Multiple Myeloma, run by Novartis Pharmaceuticals at 13 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 study is designed to assess the effectiveness of the combination of Panobinostat plus Bortezomib and Dexamethasone in patients with relapsed and bortezomib refractory Multiple Myeloma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
panobinostat, bortezomib and dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
13 sitesUnited States
Study dates
Jun 2010to Feb 2014
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

  • Patient has a previous diagnosis of multiple myeloma, based on IMWG 2003 definitions. All three of the following criteria must have been met:
  • Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation on serum or on total 24 hour urine
  • Bone marrow (clonal) plasma cells ≥ 10% or biopsy proven plasmacytoma
  • Related organ or tissue impairment (CRAB symptoms: anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections)
  • Patient must have relapsed and refractory MM and must require treatment for the relapsed disease
  • Patients must have received at least 2 prior lines of therapy which include an IMiD (thalidomide or lenalidomide)
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  • Patient must be refractory to the last bortezomib containing line of therapy given in the relapsed and refractory setting defined as:
  • having progressed on or within 60 days of the last bortezomib-containing line of therapy
  • Patient has measurable disease on M protein at study screening defined by at least one of the following measurements as per thresholds clarified in IMWG 2003 disease definitions (Kyle, et al 2003):
  • Serum M-protein ≥ 1 g/dL (≥ 10 g/L)
  • Urine M-protein ≥ 200 mg/24 h
  • Patients treated with local radiotherapy with or without concomitant exposure to steroids for pain control or management of cord/nerve root compression, are eligible. Two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and 2 weeks have passed since the last date of therapy
  • Patient's age is ≥ 18 years at time of signing the informed consent
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2
  • Patient has the following laboratory values within 3 weeks before starting study drug (lab tests may be repeated, as clinically indicated, to obtain acceptable values before screen fail is concluded but supportive therapies are not to be administered within the week prior to screening tests for absolute neutrophil count or platelet counts)
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L
  • Platelet count ≥ 70 x 109 /L
  • Serum potassium, magnesium, phosphorus, within normal limits (WNL) for institution
  • Total calcium (corrected for serum albumin) or ionized calcium ≥ LLN, and not higher than CTCAE grade 1 in case of elevated value
  • Note: Potassium, calcium, magnesium, and/or phosphorus supplements may be given to correct values that are < LLN:
  • AST/SGOT and ALT/SGPT ≤ 2.5 x ULN
  • Serum total bilirubin ≤ 1.5 ULN (or ≤ 3.0 x ULN if patient has Gilbert syndrome)
  • Serum creatinine levels ≤ 2.5 x ULN, or calculated creatinine clearance ≥ 40 ml/min
  • Patient has provided written informed consent prior to any screening procedures
  • Patient is able to swallow capsules
  • Patient must be able to adhere to the study visit schedule and other protocol requirements
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at within 7 days prior to start of study treatment

Who cannot join

  • Primary refractory disease (patients that never reached at least an MR for over 60 days under any prior therapy)
  • Patients who have a history of prior MM treatment with a DAC inhibitor including panobinostat
  • Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy
  • Peripheral neuropathy ≥ CTCAE grade 2
  • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to the first administration of study drug / treatment or who cannot be switch to safely to alternative anti-epileptic medication
  • Patients who have impaired cardiac function including any of the following:
Show all 22Show fewer
  • Congenital long QT syndrome, complete left bundle branch block or use of a permanent cardiac pacemaker, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (< 50 beats per minute). Right bundle branch block + left anterior hemiblock (bifascicular block)
  • QTcF > 450 msec on screening ECG
  • Presence of unstable atrial fibrillation. Patients with stable atrial fibrillation are allowed in the study provided they do not meet other cardiac or prohibited drug exclusion criteria
  • Previous history of angina pectoris or acute MI within 6 months
  • Congestive heart failure (New York Heart Association functional classification III-IV)
  • Patient has any other clinically significant cardiovascular disease (e.g. uncontrolled hypertension)
  • Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or significant small bowel resection)
  • Patient has unresolved diarrhea ≥ CTCAE grade 2
  • Patients who have any other concurrent severe and/or uncontrolled medical condition(s) including, but not limited to: uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease (e.g. dyspnea at rest from any cause), symptomatic thyroid dysfunction, significant bleeding tendency, that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients who are using medications that have a known relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Women who are pregnant or breast feeding
  • Patients with evidence of another malignancy not in remission or history of such a malignancy within the last 5 years (except for treated basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Patients who have received prior to starting study treatment either radiation therapy to > 30% of marrow-bearing bone within 4 weeks; myelotoxic chemotherapy within 4 weeks; or immunotherapy within 8 weeks; or who have not yet recovered from side effects of such therapies
  • 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
  • Use of chemo-, biologic or immunologic therapy and/or other investigational agents while the patient is on study treatment.
  • Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted only if commenced prior to the start of screening period)

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Emory University School of Medicine/Winship Cancer Institute Dept. of Winship Cancer Inst.

    Atlanta, Georgia, 30322

  • Georgia Regents University MedCollege of GA Cancer Ctr 2

    Augusta, Georgia, 30912

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Duke University Medical Center Dept. of DUMC (4)

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center/University of Texas MD Anderson CC

    Houston, Texas, 77030

  • University of California at Los Angeles

    Los Angeles, California, 90095

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University Medical Center, Clinical Trials Center Vanderbilt UMC

    Nashville, Tennessee, 37212

  • Hematology/Oncology of the North Shore Orchard Healthcare Res. Inc.

    Skokie, Illinois, 60076

  • Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)

    Somerset, New Jersey, 08873

  • Stanford University Medical Center Division of Hematology

    Stanford, California, 94305-5826

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

About this study

Official title: A Phase II, Multi-center, Single Arm, Open Label Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma

This study is designed to assess the effectiveness of the combination of Panobinostat plus Bortezomib and Dexamethasone in patients with relapsed and bortezomib refractory Multiple Myeloma.

Read the detailed description

This is a phase II, two stage, single arm, open label, multi-center study of oral PAN in combination with BTZ/Dex in patients with relapsed and refractory multiple myeloma, who are bortezomib-refractory and have received at least 2 prior lines of therapy. Patients must have been exposed to an iMID (lenalidomide or thalidomide) and progressed on or within 60 days of their last BTZ-containing line of therapy.

Being tested
panobinostat, bortezomib, dexamethasone
Keywords
Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma
Medical subject headings
Recurrence, 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, PAN

    PAN 20 mg PO given TIW, weeks 1\&2 of each 3-week cycle;• BTZ 1.3 mg/m2 IV push given BIW weeks 1\&2 of each 3 week cycle (days 1,4,8 and 11);• Dex 20 mg PO given QIW, weeks 1\&2 of each 3-week cycle (days 1,2,4,5,8,9,11 and 12)

  • bortezomibDrug

    Also called BTZ

  • dexamethasoneDrug

    Also called DEX

Study groups in NCT01083602
Study groupRoleWhat they receive
panobinostat + bortezomib & dexamethasoneExperimentalpanobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma
Receives: Drug: panobinostat; Drug: bortezomib; Drug: dexamethasone

What is being measured

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

  1. Overall Response Rate (PR+nCR+CR)

    Overall response rate=(PR+nCR+CR) CR= < 5% plasma cells in bone marrow. No confirmation on bone marrow plasma cell (additional assessment) is needed to document CR except patients with non-secretory myeloma where the bone marrow examination must be repeated after an interval of at least 6 weeks, Absence of M-protein in serum and urine by immunofixation,nCR same as CR without out Absence of M-protein in serum and urine by immunofixation,PR+ 50% reduction of serum M-protein and sofft tissue Plasmacytomas all for more than 6 weeks.

    Measured: after eight cycyles of treatment (24 weeks)

Secondary outcomes (5)

  1. Responders to Treatment

    The primary endpoint for this phase II study of patients with bortezomib-refractory MM is response after a maximum of 8 cycles of therapy as defined by the modified EBMT criteria.

    Measured: after eight cycyles of treatment (24 weeks)

  2. Time to Response (Greater Than or Equal to PR) Based on Investigator Assessment

    Time to response is defined as the time from the date of first administration of study treatment to the date of first documented evidence of CR or nCR or PR (whichever status is recorded first). Patients who do not have a response of PR or better by the data cut-off date are censored.

    Measured: after eight cycyles of treatment (24 weeks)

  3. Progression-free Survival

    Progression-free survival (PFS) was defined as the time from the date of first study treatment to first occurrence of documented progressive disease /relapse or death. Time from randomization until disease progression or death by Kaplan-Meier estimates

    Measured: 24 weeks

  4. Time to Progression

    Time from randomization until objective tumor progression; does not include deaths-- Kaplan-Meier estimates

    Measured: 24 weeks

  5. Over All Survival

    Kaplan Meier estimates- median time to event

    Measured: 24 weeks

Timeline

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

  1. First posted10 Mar 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

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
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01083602
Sponsor's protocol ID
CLBH589DUS71
Acronym
MACS1271
Status last verified
Nov 2017
First submitted
8 Mar 2010
Last updated
21 Dec 2017
Data monitoring committee
No

Publications

  • Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. doi: 10.1182/blood-2013-01-481325. Epub 2013 Aug 15.

    PubMed 23950178

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing panobinostat, bortezomib and dexamethasone in people with Relapsed and Bortezomib Refractory Multiple Myeloma and Refractory Multiple Myeloma, run by Novartis Pharmaceuticals at 13 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 27 inclusion and 22 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 21 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 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 27 Mar 2015). 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?

Overall Response Rate (PR+nCR+CR) (time frame: after eight cycyles of treatment (24 weeks)). 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 NCT01083602, 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 21 Dec 2017.

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