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

NCT ID: NCT00561418

Last Updated: 2015-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2013-05-31

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.

Conditions

Lymphoma; Small Intestine Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

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.

Correlative studies

Intervention Type: OTHER

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.)

Interventions

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.

Intervention Type: DRUG

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.)

Intervention Type: OTHER

Other Intervention Names

SAHA

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Ohio State University Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Craig Hofmeister

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Craig C. Hofmeister, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25213183 (View on PubMed)

Related Links

http://cancer.osu.edu

Jamesline

Other Identifiers

NCI-2011-03145

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-07047

Identifier Type: -

Identifier Source: org_study_id