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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01004991
• Other study ID #: 0907010513
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 29, 2009
• Last updated: February 3, 2017
• Start date: January 2010
• Est. completion date: February 2016

Study information

• Verified date: February 2017
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2016
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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
• vincristine
1.4 mg/m2 on Day 8 of each of 6 cycles
• doxorubicin
50 mg/m2 on Day 8 of each of 6 cycles
• prednisone
100 mg PO days 8-12 of each of 6 cycles
• 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

Locations

Country	Name	City	State
United States	Weill Cornell Medical College	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		6 months
Secondary	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.		36 months

External Links

•   Link