Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory Diffuse Large b Cell Lymphoma (DLBCL)

NCT01120834 | Completed Phase 1 Results

• 1 other identifier: 0912010795
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a phase I/II study of 5-azacitidine in combination with vorinostat in patients with relapsed or refractory DLBCL. Combination therapy with methyltransferase inhibitors and histone deacetylase inhibitors is highly synergistic in DLBCL cells, and both classes of drugs can also synergize powerfully with standard anti-lymphoma chemotheraputics such as doxorubicin in pre-clinical studies. We hypothesize that azacytidine + vorinostat combination therapy will be safe and effective in selected patients with relapsed or refractory DLBCL. We also hypothesize that patients demonstrating objective responses to this combination therapy display specific epigenetic signatures, and that a biomarker or gene classifier can be generated which will identify those patients likely to respond.

Conditions

Lymphoma

Keywords

diffuse large b cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  Overall Response Rate (ORR)

  2 cycles

Study Arms (1)

all subjects

EXPERIMENTAL

Drug: azacytidine; Drug: vorinostat

Interventions

azacytidine DRUG

* Dose level 1: azacitidine 55 mg/m2 on days 1-5 * Dose level 2: azacitidine 75 mg/m2 on days 1-5 * Dose level 3: azacitidine 55 mg/m2 on days 1-5 * Dose level 4: azacitidine 75 mg/m2 on days 1-5 Each cycle = 28 days. Subjects may receive up to 6 cycles.

all subjects

vorinostat DRUG

* Dose level 1: oral vorinostat at 300 mg BID on Days 1-7. * Dose level 2: oral vorinostat at 200 mg BID on Days 1-7. * Dose level 3: oral vorinostat at 300 mg BID on Days 1-14. * Dose level 4: oral vorinostat at 200 mg BID on Days 1-14. Each cycle = 28 days. Subjects receive up to 6 cycles.

all subjects

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed diffuse large B cell lymphoma, relapsed after or resistant to prior systemic therapy.
• Subjects must have measurable disease on cross sectional imaging that is at least 1.5 cm in diameter.
• Patients should have relapsed following or be deemed ineligible for autologous stem cell transplantation. There is no limit to number of prior therapies.
• Age \> = 18 years.
• ECOG performance status \< = 2.
• Patients must have normal organ and marrow function as defined below:
• ANC \> = 1,000/uL
• platelets \> = 75,000//uL
• total bilirubin \< = 2 X upper limit of normal
• AST(SGOT)/ALT(SGPT) \< = 2.5 X upper limit of normal
• Serum creatinine \< = 1.5 X upper limit of normal (ULN)
• Women of childbearing potential must have a negative serum pregnancy test prior to treatment
• The effects of these investigational agents on the developing human fetus at the recommended therapeutic doses are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A woman who becomes pregnant while participating in the study must withdraw from the study immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Prior allogeneic transplant
• Patients may not be receiving any other investigational agents.
• Patients may not have previously received anti-lymphoma therapy with an HDAC inhibitor (.e.g. Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid). Patients who have received an HDAC inhibitor for another indication such as epilepsy may enroll after a 30-day washout period
• Patients with known active CNS lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible..
• Patients with known hypersensitivity to azacytidine, vorinostat or mannitol.
• Patients with a currently active second malignancy.
• Uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Azacitidine; 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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Peter Martin, MD
• Organization: Weill Cornell Medicine

amr2017@med.cornell.edu

646.962.2064

Study Officials

• Peter Martin, MD

  Weill Medical College of Cornell University

  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: SPONSOR

Study Record Dates

• First Submitted: April 19, 2010
• First Posted: May 11, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: October 20, 2016
• Last Updated: April 10, 2017
• Results First Posted: April 10, 2017

Record last verified: 2017-02

Locations

US (1)