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

The Ohio State University

Status and phase

Completed

Phase 1

Conditions

Multiple Myeloma

Plasma Cell Neoplasm

Treatments

Drug: lenalidomide

Drug: vorinostat

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00729118

OSU-08001

NCI-2011-03140 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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)