Phase-II study on the value of post-transplant Cyclophosphamide after Thiotepa-based haplo-identical stem-cell transplantation for relapsed-refractory lymphoma
Organizational Data
- DRKS-ID:
- DRKS00009880
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2016-11-30
- Last update in DRKS:
- 2021-08-27
- Registration type:
- Prospective
Acronym/abbreviation of the study
CHARLY
URL of the study
No Entry
Brief summary in lay language
In order to eliminate the lymphoma disease after a relapse in the long term, a transplant with blood stem cells is recommended which has been taken from a suitable donor. Typically, 10 features are examined to identify a suitable donor. Often, however, no donor is found with complete agreement of the 10 crucial tissue features. However, there is the possibility of carrying out the transplant with a related donor in which there is no agreement for some of the relevant characteristics (so-called haplo-identical stem cell transplantation). Due to the greater deviation between the tissue characteristics, a stronger reaction between the immune system of the donor and that of the recipient is to be expected in haplo-identical stem cell transplantation, which can lead to life-threatening complications in the patient. Therefore, an effective suppression of the immune system (immunosuppression) is necessary in order to keep the dispute between the immune systems of the donor and the recipient as low as possible. The drug cyclophosphamide, which has already been used worldwide in hundreds of patients with leukemia diseases within the framework of a haplo-identical stem cell transplant, has proved particularly promising in this situation. With cyclophosphamide, the haplo-identical stem cell transplantation could achieve the same results as transplantation of precisely matched donors in this patient group. Even in patients with lymphoma, initial results indicate that the haplo-identical transplantation with cyclophosphamide could be just as safe and effective as a transplant from a fully-fitting donor. However, the overall experience with this type of immunosuppression to haplo-identical transplantation in patients with lymphoma is still limited. The aim of this study is therefore to investigate immunosuppression in patients with lymphoma and to confirm the first positive experiences in this field.
Brief summary in scientific language
Allogeneic hematopoietic stem cell transplantation (HSCT) is a valuable treatment option with curative potential for patients with relapsed and refractory non-Hodgkin lymphoma (NHL), including patients with relapse after autologous stem cell transplantation. However, matched related or unrelated donors are not always available or cannot be identified in an appropriate time frame. Since virtually every patient has a suitable haplo-identical related donor, a successful strategy for haplo-identical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) would eliminate the problem of the lack of donors. Moreover, registry analyses suggest that haplo-HSCT based on post-transplant high-dose cyclophosphamide as GVHD prophylaxis yields disease control and non-relapse mortality rates similar to sibling (SIB) and well matched unrelated donor (WMUD) transplants.(Dietrich et al., 2015) Therefore we want to study the safety and efficacy of immunosuppression with high-dose cyclophosphamide following myeloablative haplo-HSCT in poor-risk NHL in a prospective multicenter setting.
Health condition or problem studied
- ICD10:
- C85.9 - Non-Hodgkin lymphoma, unspecified
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- cyclophosphamide, 50 mg/kg (infusion), day +3 und +4 after haplo-identical allogeneic hematopoietic stem cell transplantation (haplo-HSCT)
Endpoints
- Primary outcome:
- Rate of progression-free survival (PFS) at one year post haplo-HSCT
- Secondary outcome:
- - PFS over time - OS at 12 months post HSCT - Non-relapse mortality (NRM) at 12 months post HSCT - OS over time - Clinical response (NCI criteria) measured at day 100 after haplo-HSCT - Rate of acute GVHD - Rate of cGVHD
Study Design
- Purpose:
- Treatment
- Allocation:
- N/A (single arm study)
- Control:
-
- Uncontrolled/single arm
- Phase:
- II
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Single (group)
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Multicenter study
- Recruitment location(s):
-
- University medical center Innere Medizin, Medizinische Klinik 1 Freiburg im Breisgau
- Medical center II. Medizinische Klinik Augsburg
- University medical center Medizinische Klinik I Dresden
- Medical center Klinikum München-Schwabing, 1. Med. Klinik München
- University medical center Med. Klinik II, Hämatologie und Onkologie Frankfurt a.M.
- University medical center Klinik für Innere Med. IV Halle Saale
- University medical center Med. Klinik V, Hämatologie und Onkologie Heidelberg
- University medical center Klinik für Hämatologie, Onkologie und klinische Immunologie Düsseldorf
- University medical center Medizinische Klinik A Münster
- University medical center III. Medizinische Klinik Mainz
- University medical center Campus Großhadern, Med. Klinik III München
- Medical center Helios Klinikum Berlin-Buch, Klinik für Hämatologie und SZT Berlin
Recruitment period and number of participants
- Planned study start date:
- 2017-01-01
- Actual study start date:
- 2017-05-16
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 49
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- 65 Years
- Additional Inclusion Criteria:
- 1. Written informed consent obtained according to international guidelines and local laws; 2. Male or female patients aged 18-65 years; 3. Diagnosis of one the following NHL subtypes (PTCL, DLBCL, MCL, FL, transformed CLL) 4. Refractoriness or early relapse (<12 months) after at least two regimens and/or auto-HSCT failure; 5. Intent-to Thiotepa based myeloablative Haplo-HSCT because of unavailability of a fully matched SIB or MUD (10/10), within the time frame for successful HSCT as determined by disease activity; 6. Eligible to undergo myeloablative allogeneic stem cell transplantation as judged by the treating transplant physician. E.g. patients with controlled clinically insignificant infections are eligible, whereas patients with active uncontrolled infections are not eligible. 7. ECOG performance status of 0 - 1; 8. Ability to understand the nature of the trial and the trial related procedures and to comply with them.
Exclusion Criteria
1. Patients with known congestive heart failure NYHA Class III and IV 2. Known HIV infection, infectious hepatitis (type B or C) or any other uncontrolled severe infection, i.e. patients with positive HIV test or active hepatitis B should be excluded. Only patients positive for anti-HBs+ with or without anti-HBc+ are allowed to enter the study. Patients with hepatitis C (anti-HCV+) should be excluded; 3. Known hypersensitivity to cyclophosphamide; 4. Renally impaired patients with creatinine clearance < 30 ml/min (Cockcroft-Gault equation); 5. Simultaneous participation in other clinical trials; 6. Participation in a clinical trial within the last 14 days before the date of registration of this trial; 7. Known abuse of medication, drugs or alcohol; 8. Female patients who are pregnant or breast feeding; 9. Fertile patients refusing to use safe contraceptive methods during the study. 10. Patients with uninary outflow obstructions or clinical signs of cystitis are not eligible.
Addresses
Primary Sponsor
- Address:
- Universitätsklinikum HeidelbergIm Neuenheimer Feld 67269120 HeidelbergGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.klinikum.uni-heidelberg.de
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum HeidelbergInnere Medizin VDr. med. Sascha DietrichIm Neuenheimer Feld 41069120 HeidelbergGermany
- Telephone:
- + 49 6221 56 39894
- Fax:
- + 49 6221 56 33843
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- Universitätsklinikum HeidelbergInnere Medizin VDr. med. Sascha DietrichIm Neuenheimer Feld 41069120 HeidelbergGermany
- Telephone:
- + 49 6221 56 39894
- Fax:
- + 49 6221 56 33843
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Principal Investigator
- Address:
- Universitätsklinikum HeidelbergInnere Medizin VDr. med. Sascha DietrichIm Neuenheimer Feld 41069120 HeidelbergGermany
- Telephone:
- + 49 6221 56 39894
- Fax:
- + 49 6221 56 33843
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Commercial (pharmaceutical industry, medical engineering industry, etc.)
- Address:
- Riemser Pharma GmbHAn der Wiek 717493 GreifswaldGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Medizinischen Fakultät HeidelbergAlte Glockengießerei 11/169115 HeidelbergGermany
- Telephone:
- +49-6221-338220
- Fax:
- +49-6221-3382222
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2016-05-30
- Ethics committee number:
- AFmu-313/2016
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2016-10-25
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- 2015-003920-30
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry