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

• ClinicalTrials.gov Identifier: NCT00729118
• Recruitment Status: Completed
• First Posted: August 7, 2008
• Last Update Posted: May 18, 2020
• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Yvonne Efebera, Ohio State University Comprehensive Cancer Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Multiple Myeloma; Plasma Cell Neoplasm	Drug: lenalidomide; Drug: vorinostat	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Vorinostat (SAHA) and Lenalidomide After Autologous Transplant for Patients With Multiple Myeloma
• Actual Study Start Date: September 26, 2008
• Actual Primary Completion Date: December 26, 2019
• Actual Study Completion Date: May 4, 2020

Arms and Interventions

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: 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

Outcome Measures

Primary Outcome Measures :

1. Safety of patients receiving SAHA and lenalidomide following autologous PBSCT [ Time Frame: up to 3 years ]
   Patients will be assessed for Adverse events using the NCI CTCAE version 4.0 criteria

Secondary Outcome Measures :

1. Duration of response [ Time Frame: up to 3 years ]
   The time from progression to death
2. Time to progression (TTP) [ Time Frame: up to 3 years ]
   Patients will be assessed for TTP from the start of treatment until the date of progression.
3. Progression-free survival (PFS) [ Time Frame: up to 3 years ]
   PFS is the time from the first dose a patient receives until disease progression or death at trial closure.
4. Time to response [ Time Frame: up to 3 years ]
   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.
5. Duration of overall response [ Time Frame: up to 3 years ]
   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
6. Overall survival [ Time Frame: up to 3 years ]
   The survival time defined as the time from start of treatment to the date of death.
7. Response rate [ Time Frame: up to 3 years ]
   Tumor response defined as the total number of patients whose best response is PR or CR or SD, divided by the number of patients

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Ohio State University Comprehensive Cancer Center

Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Yvonne C. Efebera, MD; Ohio State University Comprehensive Cancer Center

More Information

Additional Information:

Jamesline 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Yvonne Efebera, Principal Investigator, Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00729118
• Other Study ID Numbers: OSU-08001; NCI-2011-03140 ( Registry Identifier: Clinical Trial Reporting Program (CTRP) )
• First Posted: August 7, 2008
• Last Update Posted: May 18, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Yvonne Efebera, 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; Lenalidomide; Vorinostat; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action