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

Vorinostat (SAHA) and Lenalidomide After Autologous Transplant for Patients With Multiple Myeloma

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Plasma Cell Neoplasm
• Intervention / Treatment: Drug: lenalidomide; Drug: vorinostat

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

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:

• 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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: CC-5013; Revlimid; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of patients receiving SAHA and lenalidomide following autologous PBSCT	Patients will be assessed for Adverse events using the NCI CTCAE version 4.0 criteria	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	The time from progression to death	up to 3 years
Time to progression (TTP)	Patients will be assessed for TTP from the start of treatment until the date of progression.	up to 3 years
Progression-free survival (PFS)	PFS is the time from the first dose a patient receives until disease progression or death at trial closure.	up to 3 years
Time to response	From the first dose of study therapy until measurement criteria are first met progressive response (PR), complete response (CR) or stable disease (SD). The patients best response is recorded.	up to 3 years
Duration of overall response	The duration computed for subjects whose best response is either PR or CR or SD and is measured when first met for complete or partial response(whichever comes first) until first date of progressive disease or death	up to 3 years
Overall survival	The survival time defined as the time from start of treatment to the date of death.	up to 3 years
Response rate	Tumor response defined as the total number of patients whose best response is PR or CR or SD, divided by the number of patients	up to 3 years

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Yvonne C. Efebera, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

General Publications

• Sborov DW, Benson DM, Williams N, Huang Y, Bowers MA, Humphries K, Efebera Y, Devine S, Hofmeister CC. Lenalidomide and vorinostat maintenance after autologous transplant in multiple myeloma. Br J Haematol. 2015 Oct;171(1):74-83. doi: 10.1111/bjh.13527. Epub 2015 Jun 8.

Helpful Links

• Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2008
• Primary Completion (Actual): December 26, 2019
• Study Completion (Actual): May 4, 2020

Study Registration Dates

• First Submitted: August 6, 2008
• First Submitted That Met QC Criteria: August 6, 2008
• First Posted (Estimate): August 7, 2008

Study Record Updates

• Last Update Posted (Actual): May 18, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: stage II multiple myeloma; stage III multiple myeloma; stage I multiple myeloma; refractory multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Histone Deacetylase Inhibitors; Lenalidomide; Vorinostat
• Other Study ID Numbers: OSU-08001; NCI-2011-03140 (Registry Identifier: Clinical Trial Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No