NCT00561418 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2015-07-16

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Clinical Benefit

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outcome · POSTED

Duration of Response

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outcome · POSTED

Time to Progression

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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)
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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 Names
Drug: vorinostat
Other: Correlative studies
label
Vorinostat (SAHA)
type
EXPERIMENTAL

interventions

arm Group Labels
Vorinostat (SAHA)
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.
name
vorinostat
other Names
SAHA
type
DRUG
arm Group Labels
Vorinostat (SAHA)
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.)
name
Correlative studies
type
OTHER

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 23
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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
measure
Safety and Tolerability of Vorinostat (SAHA) After Autologous Stem Cell Transplantation
time Frame
Up to 3 years

secondary Outcomes

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.
measure
Clinical Benefit
time Frame
Up to 3 years
description
Median follow up of living patients
measure
Duration of Response
time Frame
Up to 5 years
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
measure
Time to Progression
time Frame
Up to 3 years

Full 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.

Source references

references

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.
pmid
25213183
type
RESULT