Sequential Treatment of CD20-positive Posttransplant Lymphoproliferative Disorder (PTLD)
Primary Purpose
Post-transplantation Lymphoproliferative Disorder
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Rituximab
CHOP
Sponsored by
About this trial
This is an interventional treatment trial for Post-transplantation Lymphoproliferative Disorder focused on measuring 1st-line therapy, single agent rituximab, CHOP, PTLD
Eligibility Criteria
Inclusion Criteria:
- PTLD with or without EBV association, confirmed after biopsy or resection
- 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 )
Exclusion Criteria:
- 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
- Severe psychiatric disease
- Known to be HIV positive
- Missing written informed consent of the patient
Sites / Locations
- Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Qld 4102
- Hôpital Pitié-Salpétrière, Department of Hematology, 47-83 Boulevard de l'Hopital
- Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Hematology and Oncology, Augustenburger Platz 1
- Sahlgrens hospital, Department of Hematology
Outcomes
Primary Outcome Measures
number of patients with complete and partial remission
response duration
Secondary Outcome Measures
number of patients with treatment-related death
overall survival
Full Information
NCT ID
NCT01458548
First Posted
October 18, 2011
Last Updated
October 24, 2011
Sponsor
Charite University, Berlin, Germany
1. Study Identification
Unique Protocol Identification Number
NCT01458548
Brief Title
Sequential Treatment of CD20-positive Posttransplant Lymphoproliferative Disorder (PTLD)
Official Title
Treatment of Patients With Posttransplant Lymphoproliferative Disorder (PTLD) With a Sequential Treatment Consisting of Anti-CD20 Antibody Rituximab and CHOP+GCSF Chemotherapy (Including 1st+2nd Amendment)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Terminated
Why Stopped
This study had an major amendment in 12/2006 introducing risk stratified sequential treatment (RSST). The modified protocol is registered with NCT00590447.
Study Start Date
December 2002 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Charite University, Berlin, Germany
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Post-transplantation lymphoproliferative disorder (PTLD) develops in one to ten per cent of transplant recipients and can be EBV-associated. To improve long-term efficacy after rituximab monotherapy and to avoid the toxicity of CHOP seen in first-line treatment, the investigators initiated an international multicentre phase II trial to test whether the subsequent application of rituximab and four courses of three-weekly CHOP would improve the outcome of patients with PTLD: PTLD-1, sequential treatment (ST).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-transplantation Lymphoproliferative Disorder
Keywords
1st-line therapy, single agent rituximab, CHOP, PTLD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab 375 mg/m2 IV on days 1, 8, 15 and 22.
Intervention Type
Drug
Intervention Name(s)
CHOP
Intervention Description
Cyclophosphamide 750 mg/m2 IV, adriamycine 50 mg/m2 IV, vincristine 1.4mg/m2 IV, and prednisone 50mg/m2 PO every 3 weeks at days 50, 72, 94 and 116.
Primary Outcome Measure Information:
Title
number of patients with complete and partial remission
Time Frame
1 month (plus or minus 7 days) after the last cycle of chemotherapy
Title
response duration
Time Frame
from date of best response until the date of first documented progression, assessed up to 3 years
Secondary Outcome Measure Information:
Title
number of patients with treatment-related death
Time Frame
from start of treatment, assessed up to 12 months after the end of treatment
Title
overall survival
Time Frame
from start of treatment until date of death from any cause, assessed up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
PTLD with or without EBV association, confirmed after biopsy or resection
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 )
Exclusion Criteria:
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
Severe psychiatric disease
Known to be HIV positive
Missing written informed consent of the patient
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralf U Trappe, MD
Organizational Affiliation
Charite University, Berlin, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Qld 4102
City
Brisbane
Country
Australia
Facility Name
Hôpital Pitié-Salpétrière, Department of Hematology, 47-83 Boulevard de l'Hopital
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Hematology and Oncology, Augustenburger Platz 1
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Sahlgrens hospital, Department of Hematology
City
Göteborg
ZIP/Postal Code
41345
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
27992268
Citation
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.
Results Reference
derived
PubMed Identifier
22173060
Citation
Trappe R, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, Neuhaus R, Lehmkuhl H, Horst HA, Salles G, Morschhauser F, Jaccard A, Lamy T, Leithauser M, Zimmermann H, Anagnostopoulos I, Raphael M, Riess H, Choquet S; German PTLD Study Group; European PTLD Network. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol. 2012 Feb;13(2):196-206. doi: 10.1016/S1470-2045(11)70300-X. Epub 2011 Dec 13.
Results Reference
derived
Links:
URL
http://www.lymphome.de/Gruppen/DPTLDSG/Protokolle/PTLD-I/Protokoll-PTLD-I.pdf
Description
Trial Protocol
Learn more about this trial
Sequential Treatment of CD20-positive Posttransplant Lymphoproliferative Disorder (PTLD)
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