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

Sponsor

Ohio State University Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00729118

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arm

139.2

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

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

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 :

Sep 26, 2008

Actual Primary Completion Date :

Dec 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

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

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

Secondary Outcome Measures

Duration of response [up to 3 years]
The time from progression to death
Time to progression (TTP) [up to 3 years]
Patients will be assessed for TTP from the start of treatment until the date of progression.
Progression-free survival (PFS) [up to 3 years]
PFS is the time from the first dose a patient receives until disease progression or death at trial closure.
Time to response [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.
Duration of overall response [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
Overall survival [up to 3 years]
The survival time defined as the time from start of treatment to the date of death.
Response rate [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)