Vorinostat After Stem Cell Transplant in Treating Patients With High-Risk Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00561418
Recruitment Status : Completed
First Posted : November 21, 2007
Results First Posted : July 16, 2015
Last Update Posted : July 16, 2015
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Craig Hofmeister, Ohio State University Comprehensive Cancer Center

Brief Summary:

RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth, and may stimulate the immune system to stop cancer cells from growing.

PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat after stem cell transplant in treating patients with high-risk lymphoma.

Condition or disease Intervention/treatment Phase
Lymphoma Small Intestine Cancer Drug: vorinostat Other: Correlative studies Phase 1

Detailed Description:



  • To assess dose-limiting and nonhematologic toxicity of prolonged administration of vorinostat (SAHA) when administered after autologous peripheral blood stem cell transplantation in patients with high-risk lymphoma.


  • To determine, preliminarily, clinical activity by assessing the overall survival and progression-free survival.
  • To evaluate the effect of vorinostat on immune reconstruction and acetylation.
  • To obtain pilot data regarding an association of vorinostat with patient quality of life and inflammatory cytokine production of peripheral blood mononuclear cells.

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

Approximately 60 days after autologous hematopoietic stem cell transplantation (HSCT), patients receive oral vorinostat once daily on days 1-21. Treatment repeats every 28 days for up to 11 courses in the absence of unacceptable toxicity or disease progression.

Blood and bone marrow samples are collected periodically for laboratory correlative studies comprising immune reconstitution assays, regulatory T-cell expansion analysis, H3 and H4 acetylation by immunohistochemistry, cytokine bead array to quantify interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, tumor necrosis factor alpha and interferon gamma. Quality of life correlative studies are measured by questionnaires periodically.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma
Study Start Date : November 2007
Actual Primary Completion Date : November 2012
Actual Study Completion Date : May 2013

Arm Intervention/treatment
Experimental: Vorinostat (SAHA)
Vorinostat (SAHA) will be administered orally starting approximately day +60 post HSCT for 21 consecutive days of a 28-day cycle for up to a maximum of 11 cycles with the dose escalations.
Drug: vorinostat
Vorinostat (SAHA) will be administered orally starting approximately day +60 post HSCT for 21 consecutive days of a 28-day cycle for up to a maximum of 11 cycles.
Other Name: SAHA

Other: Correlative studies
Laboratory as well as quality of life correlative studies will be obtained at days +26 to +38 (at approximately 1 month post HSCT),days +56 to +66 (≈2 mos), and at Cycle 2 Day 1 (≈3 mos.), Cycle 3 Day 1 (≈4 mos.), Cycle 5 Day 1 (≈6 mos.),Cycle 7 Day 1 (≈8 mos.), and off study (ideally at ≈12 mos.)

Primary Outcome Measures :
  1. Safety and Tolerability of Vorinostat (SAHA) After Autologous Stem Cell Transplantation [ Time Frame: Up to 3 years ]
    NCI CTCAE version 3.0 was used to assess Adverse Events (AE) Grade 1=Mild AE Grade 2=Moderate AE Grade 3=Severe AE Grade 4=Life-threatening or disabling AE

Secondary Outcome Measures :
  1. Clinical Benefit [ Time Frame: Up to 3 years ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  2. Duration of Response [ Time Frame: Up to 5 years ]
    Median follow up of living patients

  3. Time to Progression [ Time Frame: Up to 3 years ]
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Must have received a BEAM (cytarabine, etoposide, melphalan, carmustine)-conditioned autologous stem cell transplantation for any of the following high-risk lymphomas:

    • Diffuse large B-cell lymphoma as defined by:

      • Induction failure but with response to salvage therapy
      • Relapse less than one year after completion of induction therapy
      • Elevated lactate dehydrogenase (LDH) at relapse
      • Stage III/IV disease at relapse
      • Positive PET scan after induction or salvage therapy
      • Age ≤ 75 and ≥ 60 years
    • Follicular lymphoma as defined by:

      • Progressive disease after two or more prior regimens
      • Transformed to aggressive lymphoma but still chemotherapy sensitive
      • Not felt to be a good candidate for an allogeneic transplantation
    • Hodgkin lymphoma as defined by:

      • Primary refractory disease
      • Relapse less than one year after completion of induction therapy
      • Relapse with PET-positive disease after salvage therapy
      • Relapsed refractory and not felt to be a good candidate for an allogeneic transplantation
    • Mantle cell lymphoma

      • Chemotherapy-sensitive disease after induction therapy
      • Chemotherapy-sensitive relapsed disease and not felt to be a good candidate for an allogeneic transplantation
    • T-cell non-Hodgkin lymphoma (NHL)

      • Peripheral T-cell lymphoma not otherwise specified and one or more of the following at diagnosis:

        • High LDH
        • Marrow involvement
        • Age > 60 years
        • Low platelet count
        • Relapsed chemotherapy-sensitive disease
      • Angioimmunoblastic lymphadenopathy with dysproteinemia
      • Anaplastic lymphoma kinase-negative anaplastic NHL
      • Enteropathy-associated T-cell NHL
      • Natural killer (NK)/T-cell NHL and stage III/IV disease at diagnosis
      • NK blastic NHL


  • ECOG (Eastern Cooperative Oncology Group) /WHO performance status 0-2
  • ANC (absolute neutrophil count) ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST (aspartate aminotransferase)/ALT (Alanine transaminase) ≤ 2 x upper limit of normal (ULN)
  • Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 50 mL/min
  • No severe or uncontrolled systemic illness
  • Patients must be able to swallow capsules
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use at least two adequate barrier methods of contraception during study and for 90 days after completion of study therapy
  • No other malignancy within the past 5 years other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or a malignancy considered by their physician to be at less than 30% risk of relapse
  • No congenital long QT syndrome
  • No significant history of uncontrolled cardiac disease (i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the past 6 months, or uncontrolled congestive heart failure)
  • No active bacterial, fungal, or viral infection
  • No known HIV infection
  • No active hepatitis B and/or hepatitis C infection
  • No other medical condition, including mental illness or substance abuse, deemed by the Investigator(s) to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results


  • Recovered from the majority of the toxicities from the autologous transplantation (must have returned to their pretransplant baseline or have no greater than grade I extramedullary toxicity Common Toxicity Criteria for Adverse Effects[CTCAE 3.0])
  • No prior treatment with a histone deacetylase (HDAC) inhibitor (e.g., depsipeptide, MS-275, LAQ-824, belinostat, valproic acid)
  • More than 4 weeks since prior and no concurrent class Ia, Ib, or Ic antiarrhythmic drugs
  • No other concurrent antineoplastic chemotherapy or biologic therapy
  • No concurrent radiotherapy, unless for local control of bone pain

    • Irradiated area for pain management should be as small as possible and lesions within the irradiated field cannot be used for response
  • No concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of vorinostat (SAHA)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00561418

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

Additional Information:
Publications of Results:
Responsible Party: Craig Hofmeister, Principal Investigator, Ohio State University Comprehensive Cancer Center Identifier: NCT00561418     History of Changes
Other Study ID Numbers: OSU-07047
NCI-2011-03145 ( Registry Identifier: Clinical Trial Reporting Program (CTRP) )
First Posted: November 21, 2007    Key Record Dates
Results First Posted: July 16, 2015
Last Update Posted: July 16, 2015
Last Verified: July 2015

Keywords provided by Craig Hofmeister, Ohio State University Comprehensive Cancer Center:
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult Hodgkin lymphoma
recurrent mantle cell lymphoma
adult nasal type extranodal NK/T-cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
small intestine lymphoma
anaplastic large cell lymphoma

Additional relevant MeSH terms:
Intestinal Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action