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

Primary Purpose

Lymphoma, Small Intestine Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
vorinostat
Correlative studies
Sponsored by
Ohio State University Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Ohio State University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vorinostat (SAHA)

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety and Tolerability of Vorinostat (SAHA) After Autologous Stem Cell Transplantation
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

Clinical Benefit
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.
Duration of Response
Median follow up of living patients
Time to Progression
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

Full Information

First Posted
November 20, 2007
Last Updated
July 10, 2015
Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00561418
Brief Title
Vorinostat After Stem Cell Transplant in Treating Patients With High-Risk Lymphoma
Official Title
Histone Deacetylase (HDAC) Inhibition Using Vorinostat (SAHA) After Autologous Hematopoietic Stem Cell Transplantation for High Risk Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University Comprehensive Cancer Center
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Small Intestine Cancer
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vorinostat (SAHA)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
vorinostat
Other Intervention Name(s)
SAHA
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Correlative studies
Intervention Description
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 Measure Information:
Title
Safety and Tolerability of Vorinostat (SAHA) After Autologous Stem Cell Transplantation
Description
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
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Clinical Benefit
Description
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.
Time Frame
Up to 3 years
Title
Duration of Response
Description
Median follow up of living patients
Time Frame
Up to 5 years
Title
Time to Progression
Description
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
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 (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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Craig C. Hofmeister, MD
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25213183
Citation
Hofmeister CC, Williams N, Geyer S, Hade EM, Bowers MA, Earl CT, Vaughn J, Bingman A, Humphries K, Lozanski G, Baiocchi RA, Jaglowski SM, Blum K, Porcu P, Flynn J, Penza S, Benson DM, Andritsos LA, Devine SM. A phase 1 study of vorinostat maintenance after autologous transplant in high-risk lymphoma. Leuk Lymphoma. 2015 Apr;56(4):1043-9. doi: 10.3109/10428194.2014.963073. Epub 2014 Nov 20.
Results Reference
result
Links:
URL
http://cancer.osu.edu
Description
Jamesline

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

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