Melphalan and Panobinostat in Treating Patients With Recurrent Multiple Myeloma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00743288
First received: August 27, 2008
Last updated: January 9, 2014
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma and Plasma Cell Neoplasm
Drug: melphalan
Drug: panobinostat
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Oral Melphalan Combined With LBH589 for Patients With Relapsed or Refractory Multiple Myeloma (MM)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease response as assessed by modified Bladé criteria [ Designated as safety issue: No ]
  • Safety and tolerability as assessed by the NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: July 2008
Estimated Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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 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

      • 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

    • Nonmeasurable disease (i.e., patients with nonsecretory or oligosecretory multiple myeloma) not allowed
  • 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
  • No plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome)
  • No plasma cell leukemia

PATIENT CHARACTERISTICS:

  • 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)
  • AST and 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
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No peripheral neuropathy > grade 2
  • No impaired cardiac function or clinically significant cardiac disease, including any 1 of the following:

    • 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
    • QTc > 450 msec on screening ECG
    • LVEF below normal on screening ECHO or MUGA scan
    • Right bundle branch block with left anterior hemiblock (bifascicular block)
    • Myocardial infarction or unstable angina within the past 6 months
    • Other clinically significant heart disease, including any of the following:

      • NYHA class III-IV congestive heart failure
      • Uncontrolled hypertension
      • History of labile hypertension
      • History of poor compliance with an antihypertensive regimen
  • No impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
  • No prior malignancy within the past 5 years except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix
  • No 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
  • No known positivity for HIV or hepatitis B or C
  • No severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL)
  • No significant history of non-compliance to medical regimens or unwillingness or inability to comply with instructions given by the study staff

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from all prior therapy
  • Prior localized radiotherapy allowed
  • At least 3 weeks since prior chemotherapy (≥ 6 weeks for nitrosoureas)
  • At least 3 weeks since prior corticosteroids (> 10 mg/day prednisone or equivalent)
  • More than 4 weeks since prior major surgery

    • Recent kyphoplasty allowed at investigator's discretion
  • More than 8 weeks since prior immunotherapy
  • More than 4 weeks since prior antibody therapy
  • More than 2 weeks since prior radiotherapy to > 30% of marrow-bearing bone
  • No prior panobinostat
  • No concurrent medication that risk prolonging the QT interval or inducing Torsades de Pointes
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00743288

Locations
United States, California
Comprehensive Blood and Cancer Center Recruiting
Bakersfield, California, United States, 93309-0633
Contact: Ravindranath Patel, MD    661-862-7178    jsorrow@cbccusa.com   
James R. Berenson MD, Incorporated Recruiting
West Hollywood, California, United States, 90069
Contact: Regina Swift, RN    310-623-1222    jberenson@imbcr.org   
United States, Colorado
Rocky Mountain Cancer Centers - Denver Midtown Recruiting
Denver, Colorado, United States, 80218
Contact: Karen Morris, RN    303-285-5004      
United States, Maryland
Center for Cancer and Blood Disorders Recruiting
Bethesda, Maryland, United States, 20817
Contact: Natalie Bongiorno, RN    301-571-2016    nbongiorno@ccbdmd.com   
Sponsors and Collaborators
Oncotherapeutics
Investigators
Principal Investigator: James R. Berenson, MD Oncotherapeutics
  More Information

Additional Information:
No publications provided

Responsible Party: Clinical Research & Development Manager, Oncotherapeutics
ClinicalTrials.gov Identifier: NCT00743288     History of Changes
Other Study ID Numbers: CDR0000612441, ONCOTHER-CLBH589BUS15T, LBH
Study First Received: August 27, 2008
Last Updated: January 9, 2014
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014