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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Weill Medical College of Cornell University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01004991
First received: October 29, 2009
Last updated: March 8, 2011
Last verified: March 2011
  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 1
Phase 2

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

Resource links provided by NLM:


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: January 2010
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Recruiting
New York, New York, United States, 10065
Contact: Rebecca Elstrom, MD    212-746-2063    ree2001@med.cornell.edu   
Principal Investigator: Rebecca Elstrom, MD         
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:
No publications provided

Responsible Party: Rebecca Elstrom, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT01004991     History of Changes
Other Study ID Numbers: 0907010513
Study First Received: October 29, 2009
Last Updated: March 8, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Azacitidine
Cyclophosphamide
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014