Panobinostat and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

February 13, 2013 updated by: City of Hope Medical Center

A Phase I Study Evaluating the Combination of the Deacetylase Inhibitor, LBH589 Plus the mTOR Inhibitor RAD001, in Relapsed and Refractory Adult Patients With Lymphoma

RATIONALE: Panobinostat and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving panobinostat together with everolimus may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with everolimus in treating patients with relapsed or refractory lymphoma or multiple myeloma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the safety and feasibility of combining panobinostat with everolimus in patients with recurrent or refractory lymphoma or multiple myeloma.
  • To define the maximum tolerated dose of panobinostat in combination with everolimus in these patients.

Secondary

  • To obtain preliminary data for response to this treatment regimen in these patients.
  • To perform correlative studies relevant to this treatment regimen.

OUTLINE: This is a dose-escalation study of panobinostat.

Patients receive oral panobinostat 3 days a week and oral everolimus once every other day for 4 weeks Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Blood and bone marrow samples may be collected for pharmacokinetic and correlative laboratory studies.

After completion of study treatment, patients are followed up for ≥ 4 weeks.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Medical Center
      • Pasadena, California, United States, 91105
        • City of Hope Medical Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed diagnosis of one of the following:

    • Hodgkin or non-Hodgkin lymphoma (including small lymphocytic lymphoma [SLL])

      • Any histology, including B, T, or NK/T cell allowed
    • Multiple myeloma (MM)

  • Relapsed or refractory disease

    • Patients with lymphoma must have relapsed after or be refractory to an upfront regimen (e.g., CHOP or ABVD) and a salvage regimen (e.g., ICE or ESHAP)

      • Patients with SLL should have relapsed after a fludarabine-containing regimen
    • Patients with MM must have progressed within 100 days after receiving a regimen containing bortezomib and either thalidomide or lenalidomide AND have a 25% increase in serum paraproteins, urinary light chains, or plasma cell number in the bone marrow
  • No active CNS disease

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³ (transfusion allowed in patients with biopsy-proven bone marrow involvement)
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if elevation due to leukemic involvement)
  • Serum bilirubin ≤ 1.5 times ULN
  • Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
  • Serum potassium normal
  • Serum phosphorous normal
  • Serum total calcium (corrected for serum albumin) or serum ionized calcium normal
  • Serum magnesium normal
  • TSH and free T4 normal (thyroid hormone replacement allowed)
  • Fasting serum cholesterol ≤ 300 mg/dL (or ≤ 7.75 mmol/L) AND fasting triglycerides ≤ 2.5 times ULN (elevated levels allowed provided an appropriate lipid-lowering medication has been initiated)
  • LVEF normal by MUGA or ECHO
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method (including barrier method) contraception during and for 3 months after completion of study treatment

  • No impaired cardiac function, including any of the following:

    • QTc > 450 msec by screening ECG
    • Congenital long QT syndrome
    • History of sustained ventricular tachycardia
    • History of ventricular fibrillation or torsades de pointes
    • Bradycardia, defined as heart rate (HR) < 50 beats/min (pacemaker allowed provided HR ≥ 50 beats/min)
    • Myocardial infarction or unstable angina within the past 6 months
    • NYHA class III-IV congestive heart failure
    • Right bundle branch block and left anterior hemiblock (bifascicular block)
  • No uncontrolled hypertension
  • No unresolved diarrhea > CTCAE grade 1
  • No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral agents (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • No other concurrent severe or uncontrolled medical condition
  • No other primary malignancy within the past 5 years other than curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
  • No known HIV or hepatitis C positivity
  • No significant history of non-compliance to medical regimens
  • No known hypersensitivity to everolimus, other rapamycins (e.g., sirolimus or temsirolimus), or their excipients

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior autologous or allogeneic stem cell transplantation allowed
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
  • More than 1 week since prior and no concurrent immunization with live attenuated vaccines
  • More than 4 weeks since prior valproic acid
  • No other prior histone deacetylase inhibitors

  • No concurrent chronic systemic corticosteroids or another immunosuppressive agent, other than for control of itching (as in cutaneous T-cell lymphoma)

    • Concurrent corticosteroids allowed provided patient has been on a stable dosage regimen for ≥ 2 weeks before study entry
    • Topical or inhaled corticosteroids allowed
  • No concurrent drugs that may induce torsades de pointes
  • No concurrent CYP3A4 inhibitors
  • No concurrent radiotherapy or other anticancer therapy
  • No concurrent grapefruit, grapefruit juice, or seville (sour) oranges
  • No concurrent medications that may cause QTc prolongation
  • No other concurrent investigational therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose
Time Frame: 90 days post treatment start
90 days post treatment start
Toxicity
Time Frame: 90 days post treatment start
90 days post treatment start

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic and correlative studies
Time Frame: Day 1 and Day 26 of the first cycle of treament
Day 1 and Day 26 of the first cycle of treament

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

August 19, 2009

First Submitted That Met QC Criteria

August 19, 2009

First Posted (Estimate)

August 20, 2009

Study Record Updates

Last Update Posted (Estimate)

February 15, 2013

Last Update Submitted That Met QC Criteria

February 13, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08099
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-08099 (Registry Identifier: PDQ)
  • NOVARTIS-CHNMC-08099
  • CDR0000652208 (Registry Identifier: PDQ)
  • NCI-2010-00259 (Registry Identifier: NCI CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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