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Decitabine Plus R-CHOP in Diffuse Large B-cell Lymphoma

Registration Number
NCT02951728
Lead Sponsor
Ruijin Hospital
Brief Summary

This is a Phase I/II Trial of Decitabine + R-CHOP in Diffuse Large B-Cell Lymphoma

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
58
Inclusion Criteria
  • histologically confirmed DLBCL, CD20 positive.
  • must have at least one site of measurable disease, 1.5 cm in diameter or greater.
  • has not had any previous treatment.
  • International Prognostic Index >1.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • must have laboratory test results within these ranges: Absolute neutrophil count ≥1500/mm3 Platelet count≥75,000/mm3 Serum creatinine≤1.5×upper limit of normal (ULN) Total bilirubin≤1.5×ULN. Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.

AST (SGOT) and ALT (SGPT) ≤2×ULN

  • Disease free of prior malignancies 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 Decitabine 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 Decitabine. The effects of Decitabine 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 15 to 75 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. If HbsAg positive, should check HBV DNA, DNA positive patients cannot be enrolled. If HBsAg negative but HBcAb positive (whatever HBsAb status), should check HBV DNA, DNA positive patients cannot be enrolled.
  • Known central nervous system involvement by lymphoma.
  • Known or suspected hypersensitivity to Decitabine or mannitol.
  • 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
GroupInterventionDescription
Decitabine plus R-CHOPVincristineRituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11; Decitabine will be administered intravenously at dose levels as follow in Phase 1: Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose. In phase 2, Decitabine will be administered intravenously at MTD.
Decitabine plus R-CHOPRituximabRituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11; Decitabine will be administered intravenously at dose levels as follow in Phase 1: Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose. In phase 2, Decitabine will be administered intravenously at MTD.
Decitabine plus R-CHOPDoxorubicinRituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11; Decitabine will be administered intravenously at dose levels as follow in Phase 1: Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose. In phase 2, Decitabine will be administered intravenously at MTD.
Decitabine plus R-CHOPCyclophosphamideRituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11; Decitabine will be administered intravenously at dose levels as follow in Phase 1: Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose. In phase 2, Decitabine will be administered intravenously at MTD.
Decitabine plus R-CHOPPrednisoneRituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11; Decitabine will be administered intravenously at dose levels as follow in Phase 1: Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose. In phase 2, Decitabine will be administered intravenously at MTD.
Decitabine plus R-CHOPDecitabineRituximab 375 mg/m2 IV d6; Cyclophosphamide 750mg/m2 IV d7; Doxorubicin 50mg/m2 IV d7; Vincristine 1.4 mg/m2 IV d7; Prednisone 60 mg/m2 PO d7-11; Decitabine will be administered intravenously at dose levels as follow in Phase 1: Dose level 1: Decitabine 10 mg/m2 days 1-5; Dose level 2: Decitabine 15 mg/m2 days 1-5; Dose level 3: Decitabine 20 mg/m2 days 1-5 and determine the maximum tolerated dose. In phase 2, Decitabine will be administered intravenously at MTD.
Primary Outcome Measures
NameTimeMethod
maximum tolerated doseday1 to 21

The primary endpoint for the phase I portion of the study is to determine the maximum tolerated dose of Decitabine when given in combination with a standard dose (q21 day) regimen of R-CHOP in patients with DLBCL.

complete response rate21 days after 6 cycles of treatment (each cycle is 21 days)

The primary endpoint for the phase II portion of the study will be complete response rate.

Secondary Outcome Measures
NameTimeMethod
Overall survival2 years
Overall response rate21 days after 6 cycles of treatment (each cycle is 21 days)
Event-free survival2 years
Progression-free survival2 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0Up to 30 days after completion of study treatment

Trial Locations

Locations (1)

Shanghai Ruijin Hospital

🇨🇳

Shanghai, China

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