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

NCT00561418 | Completed Phase 1 Results DMC

• 2 other identifiers: OSU-07047NCI-2011-03145
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 3 years

Secondary Outcomes (3)

• Clinical Benefit

  Up to 3 years

• Duration of Response

  Up to 5 years

• Time to Progression

  Up to 3 years

Study Arms (1)

Vorinostat (SAHA)

EXPERIMENTAL

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; Other: Correlative studies

Interventions

vorinostat 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.

Also known as: SAHA

Vorinostat (SAHA)

Correlative studies 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.)

Vorinostat (SAHA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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 RESULT

Related Links

• Jamesline

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, Extranodal NK-T-Cell; Immunoblastic Lymphadenopathy; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large-Cell, Anaplastic

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphadenopathy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Craig Hofmeister, MD
• Organization: The Ohio State University Comprehensive Cancer Center

craig.hofmeister@osumc.edu

614-293-9869

Study Officials

• Craig C. Hofmeister, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 20, 2007
• First Posted: November 21, 2007
• Study Start: November 1, 2007
• Primary Completion: November 1, 2012
• Study Completion: May 1, 2013
• Last Updated: July 16, 2015
• Results First Posted: July 16, 2015

Record last verified: 2015-07

Locations

US (1)