Vorinostat and Lenalidomide After Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00729118
First received: August 6, 2008
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Giving vorinostat together with lenalidomide may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with lenalidomide after autologous stem cell transplant in treating patients with multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Plasma Cell Neoplasm
Drug: lenalidomide
Drug: vorinostat
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vorinostat (SAHA) and Lenalidomide After Autologous Transplant for Patients With Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Time to response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Duration of overall response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: September 2008
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide + Vorinostat
Maintenance post autologous transplant
Drug: lenalidomide
combined with Vorinostat (SAHA) days 1-21 of a 28-day cycle until progression or clinically significant toxicity.
Other Names:
  • Revlimid
  • CC-5013
Drug: vorinostat
Vorinostat (SAHA) will be administered orally beginning at dose level 1 starting day +90 ±6 days after HSCT for days 1 and 15-21 of a 28-day cycle combined with lenalidomide days 1-21 of a 28-day cycle until progression or clinically significant toxicity.
Other Names:
  • SAHA
  • Suberoylanilide hydroxamic acid

Detailed Description:

OBJECTIVES:

Primary

  • To assess the dose-limiting toxicities and safety of vorinostat and lenalidomide after autologous peripheral blood stem cell transplantation in patients with multiple myeloma.
  • To evaluate the overall response rate to the combination of Vorinostat (SAHA) and lenalidomide.

Secondary

  • To evaluate the effect of this treatment regimen on natural killer cell activity and regulatory T cells in the post-transplant period.
  • To determine preliminary clinical activity of this treatment regimen by assessing overall survival and progression-free survival of these patients.
  • To obtain pilot data regarding an association between this treatment regimen and patient quality of life and circulating inflammatory cytokines.

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

Patients receive oral vorinostat alone once daily on days 1-21 in course 1. For the second and subsequent courses, patients receive oral vorinostat in combination with oral lenalidomide once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative laboratory studies. Studies include functional immune assays (T-cell and natural killer cell activity and regulatory T-cell recovery) by fluorescence activated cell sorting (FACS) or ELISPOT; analysis of inflammatory markers (cytokines and catecholamines); and analysis of global H3 and H4 acetylation by immunohistochemistry.

Quality of life is assessed periodically using the Brief Pain Inventory (Short Form), The Center for Epidemiologic Studies Depression Scale (CES-D-10), a 9-item Brief Fatigue Inventory, and the FACT-G questionnaires.

After completion of study treatment, patients are followed for at least 30 days.

  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
  • Has undergone melphalan-conditioned autologous peripheral blood stem cell transplant myeloma.

PATIENT CHARACTERISTICS:

  • ECOG/WHO performance status 0-2
  • ANC ≥ 1,000/mm³
  • Platelet count ≥ 75,000/mm³
  • Total bilirubin ≤ 2 times upper limit of normal (ULN)
  • AST and ALT ≤ 2 times ULN
  • Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 90 days after completion of study treatment
  • No blood, sperm, or ova donation during and for ≥ 4 weeks after completion of study treatment
  • Able to obtain commercially available lenalidomide via Celegene's RevAssist® program

    • Registered in the RevAssist® program
    • Willing and able to comply with the requirements of RevAssist®
  • Able to swallow capsules
  • No severe or uncontrolled systemic illness
  • No "currently active" second malignancy, other than nonmelanoma skin cancer or carcinoma in situ of the cervix

    • Patients are not considered to have a "currently active" malignancy if they completed therapy for the malignancy, are disease free from the malignancy for > 5 years, and are considered by their physician to be at < 30% risk of relapse
  • No congenital long QT syndrome
  • No drug or alcohol abuse within the past 12 months
  • No history of allergic reactions (including erythema nodosum) attributed to compounds of similar chemical or biologic composition to lenalidomide, thalidomide, or vorinostat
  • No other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the study results

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 4 weeks since prior class Ia, Ib, or Ic antiarrhythmic medication
  • No prior HDAC inhibitor-like compounds (e.g., valproic acid) as anticancer therapy
  • More than 30 days since prior HDAC inhibitor-like compounds for other indications (e.g., valproic acid for epilepsy)
  • No prior gastrointestinal surgery or other procedure that may, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs
  • No concurrent corticosteroids other than for physiologic maintenance treatment
  • No concurrent radiotherapy, unless for local control of bone pain

    • Irradiated area should be as small as possible
    • Lesions within the irradiated field cannot be used for response assessment
  • No concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and anticancer activity of the study drugs
  • No other concurrent anticancer therapy, including chemotherapy or biologic therapy
  • No other concurrent HDAC inhibitors (e.g., valproic acid)
  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: NCT00729118

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Craig C. Hofmeister, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Craig Hofmeister, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00729118     History of Changes
Other Study ID Numbers: OSU-08001, NCI-2011-03140
Study First Received: August 6, 2008
Last Updated: September 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
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
Vorinostat
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014