Clinical Trials /

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

NCT01004991

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Phase I/II Trial of R-CHOP + Azacytidine in Diffuse Large B Cell Lymphoma
  • Official Title:Phase I/II Trial of Azacytidine + R-CHOP in Diffuse Large B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 0907010513
  • NCT ID: NCT01004991

Trial Conditions

  • Diffuse Large B Cell Lymphoma

Trial Interventions

DrugSynonymsArms
cyclophosphamideAll patients
vincristineAll patients
doxorubicinAll patients
prednisoneAll patients
azacytidineAll patients

Trial 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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
All patientsExperimentalsubjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
    • cyclophosphamide
    • vincristine
    • doxorubicin
    • prednisone
    • azacytidine

Eligibility 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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:Yes
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:No
Description:

Trial Keywords