Carfilzomib Plus Panobinostat in Relapsed/Refractory Multiple Myeloma (MM)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Novartis
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01301807
First received: February 21, 2011
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose levels of carfilzomib and LBH589 (panobinostat) that can be given in combination to patients with myeloma. The safety of this drug combination will also be studied.


Condition Intervention Phase
Myeloma
Drug: Carfilzomib
Drug: Panobinostat
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1/1b Study of the Efficacy and Safety of the Combination of Panobinostat Plus Carfilzomib in Patients With Relapsed/Refractory Myeloma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    The MTD of panobinostat and carfilzomib defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT) following one cycle (28 days) of combination therapy.


Estimated Enrollment: 66
Study Start Date: August 2011
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carfilzomib + Panobinostat
Carfilzomib starting dose 20 mg/m^2 by vein over 30 minutes on days 1, 2, 8, 9, 15, and 16; Panobinostat starting dose 15 mg orally 3 times/week for first 2 weeks every 28 day cycle.
Drug: Carfilzomib

Phase I starting dose 20 mg/m^2 by vein over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28 day cycle.

Phase Ib starting dose will be the maximum recommended dose from Phase I.

Drug: Panobinostat

Phase I starting dose 15 mg by mouth three times a week for first two weeks every 28 days.

Phase Ib group starting dose will be the maximum recommended dose from Phase I

Other Name: LBH589B
Experimental: Dose Expansion - Carfilzomib + Panobinostat
Carfilzomib MTD and Panobinostat MTD from Phase I.
Drug: Carfilzomib

Phase I starting dose 20 mg/m^2 by vein over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28 day cycle.

Phase Ib starting dose will be the maximum recommended dose from Phase I.

Drug: Panobinostat

Phase I starting dose 15 mg by mouth three times a week for first two weeks every 28 days.

Phase Ib group starting dose will be the maximum recommended dose from Phase I

Other Name: LBH589B

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Relapsed/refractory MM with failure to two lines of MM treatment which must include at least one IMiD (thalidomide, lenalidomide) and proteosome inhibitor (bortezomib) and measurable levels of myeloma paraprotein in serum ( >/= 0.5 g/dl), urine ( >/= 0.2 g excreted in a 24-hour collection sample), or abnormal free light chain (FLC) ratio. Oligo or non secretory myeloma patients may be included, if there is measurable plasmacytosis in the bone marrow biopsy or measurable extramedullary disease.
  2. Male or female patients aged >/= 18 years old
  3. Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  4. Patients must meet the following laboratory criteria within 28 days of starting therapy: * Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L * Hemoglobin >/= 8 g/dl ( transfusion are permitted) * Platelet count > 70,000 cells/mm^3 for patients with < 50% of bone marrow plasma cells or platelet count > 25,000 cells/mm^3 for patients in whom > 50% of the bone marrow nucleated cells were plasma cells * aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) </= 2.5 x ULN * Serum bilirubin </= 2 x ULN
  5. ECOG Performance Status of </= 2
  6. Creatinine clearance (CrCl) >/= 30 mL/minute within 28 days prior to registration, either measured or calculated using a standard formula (eg, Cockcroft and Gault)
  7. Multiple Gated Acquisition (MUGA) or echocardiogram (ECHO) must demonstrate LVEF >/= 45%.
  8. Female patients who: Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse. Male patients, even if surgically sterilized (ie, status postvasectomy), who: Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR Agree to completely abstain from heterosexual intercourse.

Exclusion Criteria:

  1. Valproic acid for the treatment of cancer
  2. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
  3. 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) * 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. * Screening electrocardiogram (ECG) with a corrected QT interval (QTc) or QTcF > 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 (NYHA) class III or IV , uncontrolled hypertension, history of labile hypertension (e.g. blood pressure greater than 160/90), or history of poor compliance with an antihypertensive regimen)
  4. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
  5. Patients with diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
  6. 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
  7. 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
  8. Patients who have received chemotherapy within </= 2 weeks by time of cycle 1 day 1 of therapy on trial ; 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.
  9. Female patients who are lactating or have a positive serum or urine pregnancy test during the Screening period.
  10. 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.
  11. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01301807

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Jatin J. Shah, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01301807     History of Changes
Other Study ID Numbers: 2010-0733, NCI-2011-00316
Study First Received: February 21, 2011
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Relapsed/refractory multiple myeloma
RRMM
Carfilzomib
Panobinostat
LBH589B

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Panobinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014