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

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Craig Hofmeister, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00561418
First received: November 20, 2007
Last updated: August 1, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Lymphoma
Small Intestine Cancer
Drug: vorinostat
Other: Correlative studies
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety and tolerability of vorinostat (SAHA) after autologous stem cell transplantation [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical benefit [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: November 2007
Study Completion Date: May 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 C2D1 (≈3 mos.), C3D1 (≈4 mos.), C5D1 (≈6 mos.),C7D1 (≈8 mos.), and off study (ideally at ≈12 mos.)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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/WHO performance status 0-2
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Total bilirubin ≤ 1.5 mg/dL
  • AST/ALT ≤ 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 [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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00561418

Locations
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.
Investigators
Principal Investigator: Craig C. Hofmeister, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Craig Hofmeister, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00561418     History of Changes
Other Study ID Numbers: OSU-07047, NCI-2011-03145
Study First Received: November 20, 2007
Last Updated: August 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by 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:
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Vorinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014