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

NCT ID: NCT01004991

Last Updated: 2017-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2016-02-29

Brief Summary

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.

Conditions

Diffuse Large B Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

All patients

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

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

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

cyclophosphamide

Intervention Type: DRUG

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

vincristine

Intervention Type: DRUG

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

doxorubicin

Intervention Type: DRUG

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

prednisone

Intervention Type: DRUG

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

azacytidine

Intervention Type: DRUG

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

Interventions

rituximab

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

Intervention Type: BIOLOGICAL

cyclophosphamide

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

Intervention Type: DRUG

vincristine

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

Intervention Type: DRUG

doxorubicin

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

Intervention Type: DRUG

prednisone

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

Intervention Type: 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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Martin, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Other Identifiers

0907010513

Identifier Type: -

Identifier Source: org_study_id