Clinical Trials /

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

NCT02753062

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Post-Transplant Lymphoproliferative Disorder
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Bendamustine Plus Subcutaneous Rituximab in Patients With Diffuse Large B-cell Lymphoma
  • Official Title: Multicenter Phase II Study of Bendamustine Plus Subcutaneous Rituximab in Patients With Diffuse Large B-cell Lymphoma (DLBCL) Type Monomorphic Post-transplant Lymphoproliferative Disorder

Clinical Trial IDs

  • ORG STUDY ID: BR_PTLD
  • NCT ID: NCT02753062

Conditions

  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
bendamustine, rituximabsymbenda, mabtherabendamustine, rituximab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
bendamustine, rituximabExperimentalBendamustine 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.
  • bendamustine, rituximab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:complete response rate
Time Frame:6 to 8 weeks after completion of the 6th cycle of treatment.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Assess response rate
Time Frame:2 to 3 weeks (or start of next cycle) after completion of the 3rd cycle of treatment and 6 to 8 weeks after completion of the 6th cycle of treatment.
Safety Issue:
Description:
Measure:Assess event-free survival
Time Frame:the time from the 1st day of treatment to the first recording of disease-progression, relapse or death of any cause or failure to achieve CR after completion, assessed up to 96 months
Safety Issue:
Description:
Measure:Assess overall survival
Time Frame:the time from the 1st day of treatment to death of any cause or the date of last follow-up, assessed up to 96 months.
Safety Issue:
Description:
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:From the date of first drug administration until the date of the 28th days of last drug administration, assessed up to 22 weeks
Safety Issue:
Description:
Measure:Assess health-related quality of life by EORTC QLQ-C30 (3rd edition)
Time Frame:within 14 days prior to treatment start and every 12 months (± 1 months) of follow-up period until final analysis and at the time of disease progression, assessed up to 96 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Asan Medical Center

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