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Vorinostat After Stem Cell Transplant in Treating Patients With High-Risk Lymphoma
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), March 2008
First Received: November 20, 2007   Last Updated: March 27, 2009   History of Changes
Sponsor: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00561418
  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
Genetic: DNA analysis
Other: immunohistochemistry staining method
Other: immunologic technique
Other: laboratory biomarker analysis
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label
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 National Cancer Institute (NCI):

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

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

Estimated Enrollment: 24
Study Start Date: November 2007
Estimated Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00561418

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service     866-627-7616     osu@emergingmed.com    
Sponsors and Collaborators
Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Investigators
Study Chair: Craig C. Hofmeister, MD Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000575701, OSU-07047, MERCK-OSU-07047, OSU-2007C0077
Study First Received: November 20, 2007
Last Updated: March 27, 2009
ClinicalTrials.gov Identifier: NCT00561418     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Physiological Effects of Drugs
Ileal Diseases
Duodenal Neoplasms
Neoplasms by Site
Ileal Neoplasms
Jejunal Diseases
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Digestive System Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Vorinostat
Enzyme Inhibitors
Intestinal Diseases
Protective Agents
Pharmacologic Actions
Intestinal Neoplasms
Lymphatic Diseases
Neoplasms

ClinicalTrials.gov processed this record on November 30, 2009