Phase I/II Trial of R-CHOP + Azacytidine in Diffuse Large B Cell Lymphoma - Full Text View

Sponsor:	Weill Medical College of Cornell University
Collaborator:	Celgene Corporation
Information provided by:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT01004991

Purpose

This is a phase I/II open label, multi-center study of azacytidine in combination with standard RCHOP therapy in patients with DLBCL. Patients will be treated with azacytidine at escalating doses on days 1-5, followed by standard dose rituximab plus CHOP chemotherapy on day 8, every 21 days. Patients will be treated for a total 6 cycles. The phase II portion will then evaluate efficacy of the combination at the established MTD.

Condition	Intervention	Phase
Diffuse Large B Cell Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: vincristine Drug: doxorubicin Drug: prednisone Drug: azacytidine	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment
Official Title:	Phase I/II Trial of Azacytidine + R-CHOP in Diffuse Large B-Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Rituximab Azacitidine Vincristine sulfate

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:

The primary endpoint for the phase I portion of the study is to determine the maximum tolerated dose and toxicity of azacytidine when given in combination with a standard dose (q 21 day) regimen of R-CHOP in patients with DLBCL. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The primary endpoint for the phase II portion of the study will be progression-free survival(PFS), as measured from the start of the treatment to the date of either documentation of disease progression or death. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	46
Study Start Date:	October 2009
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
All patients: Experimental subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP	Biological: rituximab 375 mg/m2 on Day 8 of each of 6 cycles Drug: cyclophosphamide 750 mg/m2 on Day 8 of each of 6 cycles Drug: vincristine 1.4 mg/m2 on Day 8 of each of 6 cycles Drug: doxorubicin 50 mg/m2 on Day 8 of each of 6 cycles Drug: prednisone 100 mg PO days 8-12 of each of 6 cycles Drug: azacytidine Dose level 1: azacytidine 25 mg/m2 days 1-5 Dose level 2: azacytidine 50 mg/m2 days 1-5 Dose level 3: azacytidine 75 mg/m2 days 1-5

Arms

Assigned Interventions

All patients: Experimental

subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP

Biological: rituximab

375 mg/m2 on Day 8 of each of 6 cycles

Drug: cyclophosphamide

750 mg/m2 on Day 8 of each of 6 cycles

Drug: vincristine

1.4 mg/m2 on Day 8 of each of 6 cycles

Drug: doxorubicin

50 mg/m2 on Day 8 of each of 6 cycles

Drug: prednisone

100 mg PO days 8-12 of each of 6 cycles

Drug: azacytidine

Dose level 1: azacytidine 25 mg/m2 days 1-5 Dose level 2: azacytidine 50 mg/m2 days 1-5 Dose level 3: azacytidine 75 mg/m2 days 1-5

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have histologically confirmed DLBCL with characteristic immunophenotypic profiles. Tumor tissue must be confirmed to express the CD20 antigen by flow cytometry or immunohistochemistry.
Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
Patient has not had any previous treatment.
Stage II (not appropriate for abbreviated chemoimmunotherapy and radiotherapy), III or IV disease
Able to adhere to the study visit schedule and other protocol requirements.
Patients must have laboratory test results within these ranges:
- Absolute neutrophil count > = 1500/mm³
- Platelet count > = 75,000/mm³
- Serum creatinine < = 1.5X upper limit of normal (ULN)
- Total bilirubin < = 1.5X ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.
- AST (SGOT) and ALT (SGPT) < = 2 x ULN
Disease free of prior malignancies for > = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacitidine. The effects of azacytidine on the developing human fetus at the recommended therapeutic dose 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.
Age >18 years.
Ability to understand and the willingness to sign a written informed consent document.
ECOG performance status of 0-2

Exclusion Criteria:

Patients must not have any serious medical condition, laboratory abnormality,or psychiatric illness that would prevent the subject from signing the informed consent form.
Patients must not have any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
Use of any other experimental drug or therapy within 28 days of baseline.
Concurrent use of other anti-cancer agents or treatments.
Known positive for HIV or infectious hepatitis B.
Known central nervous system involvement by lymphoma.
Known or suspected hypersensitivity to azacitidine or mannitol.
Patients must not have advanced malignant hepatic tumors.
Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004991

Contacts

Contact: Rebecca Elstrom, MD

212-746-2063

ree2001@med.cornell.edu

Locations

United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065

Sponsors and Collaborators

Weill Medical College of Cornell University

Celgene Corporation

Investigators

Principal Investigator:

Rebecca Elstrom, MD

Weill Medical College of Cornell University

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Weill Cornell Medical College ( Rebecca Elstrom, MD )
Study ID Numbers:	0907010513
Study First Received:	October 29, 2009
Last Updated:	October 29, 2009
ClinicalTrials.gov Identifier:	NCT01004991 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Prednisone
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Lymphoma, B-Cell
Therapeutic Uses
Azacitidine

Alkylating Agents
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin

ClinicalTrials.gov processed this record on February 08, 2010