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

July 10, 2015 updated by: Craig Hofmeister, Ohio State University Comprehensive Cancer Center

Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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 Names:
  • 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.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 3 years
Duration of Response
Time Frame: Up to 5 years
Median follow up of living patients
Up to 5 years
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
Up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ohio State University Comprehensive Cancer Center

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Craig C. Hofmeister, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

November 20, 2007

First Submitted That Met QC Criteria

November 20, 2007

First Posted (Estimate)

November 21, 2007

Study Record Updates

Last Update Posted (Estimate)

July 16, 2015

Last Update Submitted That Met QC Criteria

July 10, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSU-07047
  • NCI-2011-03145 (Registry Identifier: Clinical Trial Reporting Program (CTRP))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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