Bendamustine Plus Subcutaneous Rituximab in Patients With Diffuse Large B-cell Lymphoma

NCT ID: NCT02753062

Last Updated: 2016-04-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2023-08-31

Brief Summary

This is an open-label, multi-center, prospective, single arm phase 2 trial of the combination of bendamustine and rituximab in patients with PTLD, monomorphic cluster of differentiation antigen 20(CD20) positive DLBCL. The investigators want to investigate the efficacy and safety of the combination of bendamustine and rituximab in patients with previously untreated PTLD, monomorphic CD20 (+) diffuse large B-cell lymphoma.

Detailed Description

Monomorphic PTLD comprise more than 70% of PTLDs and diffuse large B-cell lymphoma is the predominant subtype. However, none of the trials have been performed for the specific population of DLBCL type monomorphic PTLD. The investigators will select Patients with proven, measurable monomorphic PTLD of DLBCL after solid organ transplantation (e.g. heart, lung, liver or kidney etc.). Patients having PTLD with or without Epstein-Barr virus (EBV) association, positive for CD20 monomorphic DLBCL type. The B-R treatment will continue up to 6 cycles with interval of 21 days. Patients will receive 375 mg/m2 on day 1 and bendamustine 120 mg/m2 by intravenous infusion on day 2 and 3 in the first cycle. From the 2nd to 6th cycle, rituximab will be administered subcutaneously at a fixed dose of 1400 mg and bendamustine 120 mg/m2 by intravenous infusion on day 1 following administration of rituximab and day 2. On the first day of infusion of bendamustine in each cycle, palonosetron 0.25 mg will be given as a single intravenous injection about 30 minutes before infusion of bendamustine. Pegfilgrastim 6 mg will be administered as a single subcutaneous injection between 24 to 48 hours after completion of chemotherapy at each cycle. Based on relatively good safety profile and efficacy of bendamustine and rituximab (BR regimen), the investigators will investigate a feasibility of BR regimen in this immunocompromised patients with DLBCL type monomorphic PTLD.

Conditions

Diffuse Large B Cell Lymphoma

Study Design

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

Study Groups

bendamustine, rituximab

Bendamustine plus subcutaneous Rituximab treatment of 6 cycles. Rituximab 1400mg subcutaneous over 5mins on day 1 and bendamustine 120mg/m2 + NS 500mL iv over 1hour on day 1 and 2.

Group Type: EXPERIMENTAL

bendamustine, rituximab

Intervention Type: DRUG

subjects will receive rituximab 375mg/m2 on day 1 and bendamustine 120mg/m2 by intravenous infusion on day 2 and 3 in the first cycle. From the 2nd to 6th cycle, rituximab will be administered subcutaneously at a fixed dose of 1400mg and bendamustine 120mg/m2 by intravenous infusion on day 1 following administration of rituximab and day 2.

Interventions

bendamustine, rituximab

subjects will receive rituximab 375mg/m2 on day 1 and bendamustine 120mg/m2 by intravenous infusion on day 2 and 3 in the first cycle. From the 2nd to 6th cycle, rituximab will be administered subcutaneously at a fixed dose of 1400mg and bendamustine 120mg/m2 by intravenous infusion on day 1 following administration of rituximab and day 2.

Intervention Type: DRUG

Other Intervention Names

symbenda, mabthera

Eligibility Criteria

Inclusion Criteria

1. Written informed consent

2. Histologically confirmed adult patients diagnosed with CD20-positive monomorphic PTLD, DLBCL irrespective of EBV association

3. Patients having undergone solid organ transplantation (heart, lung, liver, kidney, pancreas, small intestine transplantation, etc or a combination of the organ transplantations mentioned).

4. No prior treatment for PTLD, DLBCL except reduction of immunosuppression

5. At least one measurable lesion ≥ 1.5 cm in greatest transverse diameter by spiral CT

6. Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2.

7. Age ≥ 19

8. Adequate renal function: serum creatinine level < 2.0 mg/dL

9. Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value (or < 5 x ULN in the presence of DLBCL involvement of the liver), bilirubin < 2 X upper normal value (or < 5 x ULN in the presence of DLBCL involvement of the liver)

10. Adequate hematological function: hemoglobin ≥ 9.0 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone marrow involvement by lymphoma. (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment).

11. Life expectancy 6 months

12. A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause.

13. Female patients of child bearing potential must use an effective method of birth control (i.e. hormonal contraceptive, intrauterine device,diaphragm with spermicide, condom with spermicide or abstinence) during treatment period and 12 month thereafter; Males must use an effective method of birth control during treatment period and 12 months thereafter.

Exclusion Criteria

1. Other subtypes PTLD than monomorphic CD20 (+) DLBCL

2. Previous treatment for PTLD, DLBCL with immunotherapy or chemotherapy except for short-term corticosteroids (duration of ≤ 8 days) before inclusion (Low dose steroid as immunosuppressant are allowed.)

3. central nervous system (CNS) involvement by lymphoma or any evidence of spinal cord compression.

4. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin, early gastric cancer or carcinoma in situ of the cervix or breast or untreated prostatic cancer without any plan for a treatment) unless the patient has been free of the disease for ≥ 3 years

5. Patients with a known history of HIV or HCV seropositivity.

6. Patients with active hepatitis B i. HBsAg positive or ii. HBsAg negative, anti-HBc-Ab positive and HBV-DNA PCR positive patients

7. Pregnant or lactating women

8. Men who are not surgically sterile or women of childbearing potential not employing adequate contraception

9. Other serious illness or medical conditions i. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months ii. History of significant neurological or psychiatric disorders including dementia or seizures iii. Active, uncontrolled infections requiring systemic antibiotic therapy or other serious infections within 14 days before study enrollment iv. Other serious medical illnesses

10. Known hypersensitivity to any of the study drugs or its ingredients

11. Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cheolwon Suh

UNKNOWN

Sponsor Role: collaborator

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Dok Hyun Yoon

Assistant professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wonseog Kim, M.D., PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

Asan Medical Center

Seoul, Songpa-gu, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Dok Hyun Yoon, M.D., PhD

Role: CONTACT

dhyoon@amc.seoul.kr

82-10-3235-3090

Cheolwon Suh, M.D., PhD

Role: CONTACT

csuh@amc.seoul.kr

82-10-3735-3209

Facility Contacts

Dok Hyun Yoon, M.D.,Ph D

Role: primary

dhyoon@amc.seoul.kr

82-10-3235-3090

Cheolwon Suh, M.D.,Ph D

Role: backup

csuh@amc.seoul.kr

82-10-3735-3209

Other Identifiers

BR_PTLD

Identifier Type: -

Identifier Source: org_study_id