Diffuse Large B Cell Lymphoma
Conditions
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.
Interventions
BIOLOGICALrituximab
375 mg/m2 on Day 8 of each of 6 cycles
DRUGcyclophosphamide
750 mg/m2 on Day 8 of each of 6 cycles
DRUGvincristine
1.4 mg/m2 on Day 8 of each of 6 cycles
DRUGdoxorubicin
50 mg/m2 on Day 8 of each of 6 cycles
DRUGprednisone
100 mg PO days 8-12 of each of 6 cycles
DRUGazacytidine
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
Sponsors
Celgene
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response | 13 months | Complete Response |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients subjects will receive azacytidine dose dependent on dose-escalation schedule at time of enrollment - all will receive standard dose RCHOP
rituximab: 375 mg/m2 on Day 8 of each of 6 cycles
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 | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 65 years |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
Complete Response
Complete Response
Time frame: 13 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Patients | Complete Response | 11 Participants |