Risk Stratified Sequential Treatment for CD20-positive PTLD

NCT00590447 | Completed Phase 2

• 2 other identifiers: PTLD-1, 3rd. amendmentEudraCT 2005-000743-29
• Study Type: interventional
• Target: 152
• Locations: 7 countries
• Sites: 7

Brief Summary

This phase-II trial will investigate the efficacy, safety and the tolerability of a sequential therapy consisting of 4 courses of single agent rituximab followed by 4 courses of R-CHOP chemotherapy in patients with CD20+ posttransplant lymphoproliferative disorders (PTLD). However, responders to rituximab achieving a CR after the first 4 applications of rituximab will go on with rituximab monotherapy and will not receive chemotherapy.

Conditions

PTLD; Posttransplant Lymphoproliferative Disorder

Keywords

1st-line therapy; single agent rituximab; CHOP; risk stratification

Outcome Measures

Primary Outcomes (1)

• The primary objective is the evaluation of the efficacy.For this aim the overall objective response rates after therapy = complete and partial response and the duration of the response will be measured.

  evaluated 4 weeks after comleting therapy

Secondary Outcomes (1)

• The secondary objective is to determine the adverse events and tolerability of rituximab and/or chemotherapy. Furthermore, the long-term safety will be determined, especially the frequency of complicating infections and the overall survival.

  within 2 years of follow up

Study Arms (2)

A

EXPERIMENTAL

All patients will receive 4 courses of rituximab on days 1, 8, 15 and 22. Patients achieving a CR after the first 4 applications of single agent rituximab (evaluated between day 40 to 50) will go on with 4 further courses of single agent rituximab on days 50, 72, 94 and 116.

Drug: rituximab monotherapy

B

EXPERIMENTAL

All patients will receive 4 courses of rituximab on days 1, 8, 15 and 22. Patients who do not achieve a CR after the first 4 applications of single agent rituximab (evaluated between day 40 to 50) will go on with 4 courses of R-CHOP on days 50, 72, 94 and 116.

Drug: sequential R-CHOP

Interventions

rituximab monotherapy DRUG

375 mg/m2, IV on days 1, 8, 15, 22, 50, 72, 94 and 116. In case of disease progression during the first 4 administration of rituximab antibody or the 4 weeks interval between course 4 and 5 the patients directly enter R-CHOP chemotherapy (Arm B).

A

sequential R-CHOP DRUG

375 mg/m2 rituximab, IV on days 1, 8, 15, 22, 50, 72, 94 and 116. Cyclophosphamid 750 mg/m2, adriamycine 50 mg/m2 and vincristine 1.4mg/m2, IV and prednisone 50mg/m2, PO every 3 weeks at days 50, 72, 94 and 116. In case of disease progression during the first 4 administration of rituximab antibody or the 4 weeks interval between antibody and R-CHOP administration the patients directly enter R-CHOP chemotherapy.

B

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PTLD with or without EBV association, confirmed after biopsy or resection of tumor
• Measurable disease of \> 2 cm in diameter and/or bone marrow involvement
• Patients having undergone heart, lung, liver, kidney, pancreas, small intestine transplantation or other or a combination of the organ transplantations mentioned
• Karnofsky scale \>50% or ECOG ≤ 3
• Reduction of immunosuppression with or without antiviral therapy
• A complete surgical extirpation of tumor was not performed
• A radiation therapy was not performed
• Effective contraception for women in childbearing age
• Patient's written informed consent and written consent for data collection
• Patients are \> 18 years (or ≥ 15 years with parental agreement )

You may not qualify if:

• Life expectancy less than 6 weeks
• Karnofsky-scale \<50% or ECOG ≥ 3
• Treatment with rituximab before
• Known allergic reactions against foreign proteins
• Concomitant diseases, which exclude the administration of therapy as outlined by the study protocol
• non-compensated heart failure
• Dilatative cardiomyopathy
• Myocardial infarction during the last 6 months
• Severe non-compensated hypertension
• Severe non-compensated diabetes mellitus
• Renal insufficiency (creatinine more than 3-fold of the upper normal value), not related to lymphoma
• Hepatic insufficiency with transaminase values greater than 3-fold of the normal values and/or bilirubin levels \>3.0 mg/dl, not related to lymphoma
• Clinical signs of cerebral dysfunction
• Women during the lactation period, pregnant or of childbearing potential not using a reliable contraceptive method
• Involvement of the central nervous system by the disease

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (7)

Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Qld 4102

Brisbane, Australia

Location

Catholic University of Leuven, Department of Hematology

Leuven, Belgium

Location

Hôpital Pitié-Salpétrière, Department of Hematology, 47-83 Boulevard de l'Hopital

Paris, 75651, France

Location

Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Hematology and Oncology, Augustenburger Platz 1

Berlin, 13353, Germany

Location

Div. Universitaria Ematologia e Terapie Cellulari, University of Torino

Torino, 10128, Italy

Location

Zakład Propedeutyki Onkologii, Gdańskiego Uniwersytetu Medycznego

Gdynia, 81519, Poland

Location

Sahlgrens hospital, Department of Hematology

Gothenburg, 41345, Sweden

Location

Related Publications (1)

• Trappe RU, Dierickx D, Zimmermann H, Morschhauser F, Mollee P, Zaucha JM, Dreyling MH, Duhrsen U, Reinke P, Verhoef G, Subklewe M, Huttmann A, Tousseyn T, Salles G, Kliem V, Hauser IA, Tarella C, Van Den Neste E, Gheysens O, Anagnostopoulos I, Leblond V, Riess H, Choquet S. Response to Rituximab Induction Is a Predictive Marker in B-Cell Post-Transplant Lymphoproliferative Disorder and Allows Successful Stratification Into Rituximab or R-CHOP Consolidation in an International, Prospective, Multicenter Phase II Trial. J Clin Oncol. 2017 Feb 10;35(5):536-543. doi: 10.1200/JCO.2016.69.3564. Epub 2016 Dec 19.

  PMID: 27992268 RESULT

Study Officials

• Hanno Riess, MD

  Charité, Campus Virchow-Klinikum Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Ralf U Trappe, MD

  Charité, Campus Virchow-Klinkum, Berlin, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head German PTLD Study Group

Study Record Dates

• First Submitted: December 28, 2007
• First Posted: January 10, 2008
• Study Start: December 1, 2006
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: March 7, 2017

Record last verified: 2017-03

Locations

DE (1); IT (1); SE (1); BE (1); PL (1); AU (1); FR (1)