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

Phase 1

Completed

• Conditions: Diffuse Large B Cell Lymphoma
• Interventions: Biological: rituximab; Drug: cyclophosphamide; Drug: vincristine; Drug: doxorubicin; Drug: prednisone; Drug: azacytidine

• Registration Number: NCT01004991
• Lead Sponsor: Weill Medical College of Cornell University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-10-29
• Study First Submitted QC: 2009-10-29
• Study First Posted: 2009-10-30
• Study Start: 2010-01
• Primary Completion: 2013-09
• Study Completion: 2016-02
• Status Verified: 2017-02
• Results First Submitted: 2017-02-23
• Results First Submitted QC: 2017-02-23
• Last Update Submitted: 2017-02-23
• Results First Posted: 2017-04-10
• Last Update Posted: 2017-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
All patients	rituximab	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
All patients	cyclophosphamide	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
All patients	vincristine	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
All patients	prednisone	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
All patients	doxorubicin	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
All patients	azacytidine	subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP

Primary Outcome Measures

Name	Time	Method
Complete Response	13 months	Complete Response

Trial Locations

Locations (1)

Weill Cornell Medical College; 🇺🇸 New York, New York, United States