PTLDPhase 2PTLD-1/3NCT00590447
Risk Stratified Sequential Treatment for CD20-positive PTLD
A Phase 2 study testing rituximab monotherapy and sequential R-CHOP in people with PTLD and Posttransplant Lymphoproliferative Disorder, run by Charite University, Berlin, Germany at 7 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- PTLD, Posttransplant Lymphoproliferative Disorder
- What is being tested?
- rituximab monotherapy and sequential R-CHOP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 7 sitesin 7 countries
- Study dates
- Dec 2006to Jul 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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 )
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 7 countries.
7 sites in 7 countries
Australia1 site
Princess Alexandra Hospital, Ipswich Rd, Woolloongabba, Qld 4102
Brisbane
France1 site
Hôpital Pitié-Salpétrière, Department of Hematology, 47-83 Boulevard de l'Hopital
Paris, 75651
Germany1 site
Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Department of Hematology and Oncology, Augustenburger Platz 1
Berlin, 13353
Italy1 site
Div. Universitaria Ematologia e Terapie Cellulari, University of Torino
Torino, 10128
Poland1 site
Zakład Propedeutyki Onkologii, Gdańskiego Uniwersytetu Medycznego
Gdynia, 81519
About this study
Official title: Treatment of Patients With Posttransplant Lymphoproliferative Disorder (PTLD) With a Sequential Treatment Consisting of Anti-CD20 Antibody Rituximab and CHOP+GCSF Chemotherapy (PTLD-1/3)
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.
Read the detailed description
The rationale for performing the present study is to combine two highly active treatment modalities in first line therapy of solid organ recipients with B-cell PTLD. The monoclonal antibody CD20 represents an effective therapeutic approach in the treatment of PTLD. Unfortunately this effect seems to be of limited duration in some patients, who benefited from monotherapy with rituximab. The advantage of this therapeutic approach in PTLD is due to the low incidence of third to fourth degree adverse events. At diagnosis of PTLD a relevant proportion of these patients is not suitable for first line cytotoxic chemotherapy due to widespread disease, organ dysfunction or reduced performance state. Insufficiencies of kidney or bone marrow function are frequent in organ recipients due the toxic side effects of the immunosuppressive drugs. After pre-phase treatment with the monoclonal antibody rituximab the CHOP chemotherapy is suggested to be less toxic due to the lower tumor burden. Thereby treatment related severe or even lethal toxicities, frequently reported in patients with PTLD who underwent cytotoxic chemotherapy, may be prevented. Furthermore the total number of cytotoxic cycles of CHOP-therapy is reduced from 6 for 8 to 4 cycles and thus may result in an additional reduction of toxicity in the single patient. Because immunochemotherapy (R-CHOP) is clearly superior to CHOP with respect to progression free survival and relapse rates in patients with classical NHL and rituximab is very unlikely to add any further toxicity to CHOP the majority of patients will go on with four courses of R-CHOP. However, patients with a complete remission after 4 courses of single agent rituximab may have a very favourable risk profile and therefore will go on with rituximab single agent instead of R-CHOP.
- Conditions
- PTLD, Posttransplant Lymphoproliferative Disorder
- Being tested
- rituximab monotherapy, sequential R-CHOP
- Keywords
- 1st-line therapy, single agent rituximab, CHOP, risk stratification
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximab monotherapyDrug
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).
sequential R-CHOPDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: sequential R-CHOP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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.
Measured: within 2 years of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2008 (estimated)
- Study startDec 2006
- Primary completionDec 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTLDStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ralf Trappe, Charite University, Berlin, Germany
- Investigators
- Hanno Riess, MD, Principal investigator, Charité, Campus Virchow-Klinikum Berlin, GermanyRalf U Trappe, MD, Study chair, Charité, Campus Virchow-Klinkum, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00590447
- Sponsor's protocol ID
- PTLD-1, 3rd. amendment
- Other IDs
- EudraCT 2005-000743-29
- Acronym
- PTLD-1/3
- Status last verified
- Mar 2017
- First submitted
- 28 Dec 2007
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27992268
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Patients With Posttransplant Lymphoproliferative Disorder (PTLD) With a Sequential Treatment Consisting of Anti-CD20 Antibody Rituximab and CHOP+GCSF Chemotherapy (PTLD-1/3)
- ClinicalTrials.gov ID
- NCT00590447
- Acronym / sponsor ID
- PTLD-1/3 / PTLD-1, 3rd. amendment
- Conditions
- PTLD, Posttransplant Lymphoproliferative Disorder
- Keywords
- 1st-line therapy, single agent rituximab, CHOP, risk stratification
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Dec 2006
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 10 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The rationale for performing the present study is to combine two highly active treatment modalities in first line therapy of solid organ recipients with B-cell PTLD. The monoclonal antibody CD20 represents an effective therapeutic approach in the treatment of PTLD. Unfortunately this effect seems to be of limited duration in some patients, who benefited from monotherapy with rituximab. The advantage of this therapeutic approach in PTLD is due to the low incidence of third to fourth degree adverse events. At diagnosis of PTLD a relevant proportion of these patients is not suitable for first line cytotoxic chemotherapy due to widespread disease, organ dysfunction or reduced performance state. Insufficiencies of kidney or bone marrow function are frequent in organ recipients due the toxic side effects of the immunosuppressive drugs. After pre-phase treatment with the monoclonal antibody rituximab the CHOP chemotherapy is suggested to be less toxic due to the lower tumor burden. Thereby treatment related severe or even lethal toxicities, frequently reported in patients with PTLD who underwent cytotoxic chemotherapy, may be prevented. Furthermore the total number of cytotoxic cycles of CHOP-therapy is reduced from 6 for 8 to 4 cycles and thus may result in an additional reduction of toxicity in the single patient. Because immunochemotherapy (R-CHOP) is clearly superior to CHOP with respect to progression free survival and relapse rates in patients with classical NHL and rituximab is very unlikely to add any further toxicity to CHOP the majority of patients will go on with four courses of R-CHOP. However, patients with a complete remission after 4 courses of single agent rituximab may have a very favourable risk profile and therefore will go on with rituximab single agent instead of R-CHOP.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: rituximab monotherapyAll 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. |
| B | Experimental | Drug: sequential R-CHOPAll 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximab monotherapy375 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). | Drug | A |
| sequential R-CHOP375 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. | Drug | B |
Primary outcome
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.
Time frame: evaluated 4 weeks after comleting therapy
1 secondary outcome
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.
Time frame: within 2 years of follow up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
- Results publication: PubMed 27992268Trappe 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanno Riess, MD principal investigator
Charité, Campus Virchow-Klinikum Berlin, Germany
Ralf U Trappe, MD study chair
Charité, Campus Virchow-Klinkum, Berlin, Germany
7 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab monotherapy and sequential R-CHOP in people with PTLD and Posttransplant Lymphoproliferative Disorder, run by Charite University, Berlin, Germany at 7 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia, Belgium, France, Germany, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: evaluated 4 weeks after comleting therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00590447, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.