No registrations found.
ID
Source
Brief title
Health condition
Refractory or relapsed Chronic Lymphocytic Leukemia
Sponsors and support
P/a HOVON Data Center
Erasmus MC - Daniel den Hoed
Postbus 5201
3008 AE Rotterdam
Tel: 010 7041560
Fax: 010 7041028
e-mail: hdc@erasmusmc.nl
Intervention
Outcome measures
Primary outcome
Progression-free survival from registration with progression defined as time to:a. death due to any cause, orb. progression or relapse excluding progressive MRD triggering cessation of immunosuppression or DLI whichever comes first
Secondary outcome
- incidence and severity of tumor lysis during first course of R-DHAP;
- response to three courses of R-DHAP including SD;
- percentage of successful donor searches;
- percentage of patients who received alloSCT;
- best response on protocol;
- engraftment after alloSCT;
- incidence and severity of acute and chronic GVHD;
- toxicity;
- overall survival (OS) from registration;
- response of MRD to immunomodulation (either accelerated cessation of immunosuppression or DLI);
- response of PD to recommended off-protocol immunomodulation (either accelerated cessation of immunosuppression or DLI);
- disease status at two years after registration;
- PFS and OS after alloSCT.
Background summary
Study phase: Phase II.
Study objective:
Evaluation of the effect of salvage therapywith R-DHAP followed by reduced-intensity conditioning and allogeneic stem cell transplantation from a sibling or unrelated donor.
Patient population:
Patients with B-CLL, in need of treatment and either refractory to fludarabine, or relapsed within one year after last fludarabine gift or within two years after fludarabine combined with monoclonal antibody or refractory /relapsed and having 17p deletion and age 18-70 years and hematopoeitic stem cell transplantation comorbidity index ¡Ü2.
Study design:
Prospective, multicenter, non-randomized.
Duration of treatment:
Duration of salvage therapy at least three months, depending on donor availability; duration of stem cell transplantation and subsequent period in which immunomodulation may be applied (earlier cessation of immunosuppression or DLI) maximum two years from registration.
Study objective
The hypothesis to be tested is that reinduction treatment with at least three courses of R-DHAP followed by RIC AlloSCT is feasible and efficacy meets the expectations as described in the protocol.
Study design
At entry, after 3 courses of R-DHAP, at 3 months after SCT and thereafter at 3 or 2 months intervals until 24 months, dependingon disease status. In case no donor was found: after the last R-DHAP and then at 3, 6, 9, 12 and 24 months or until progression.
Intervention
All patients will be treated with at least three courses of R-DHAP (rituximab, dexamethasone, cisplatin, cytarabin, 4 days every 4 weeks) while a HLA-identical donor is being searched. Patients with a donor and responsive or stable disease (SD) after at least three courses R-DHAP proceed to RIC alloSCT. DLI will be given for increasing minimal residual disease (MRD) after cessation of immunosuppression. In case no suitable donor is found, responsive patients are treated with additional courses of R-DHAP until a total of 6 courses from registration on have been administered.
Department of Internal Medicine <br>
P.O. Box 5800
M. Gelder, van
Maastricht 6202 AZ
The Netherlands
+31 (0)43 3877025
mvg@sint.azm.nl
Department of Internal Medicine <br>
P.O. Box 5800
M. Gelder, van
Maastricht 6202 AZ
The Netherlands
+31 (0)43 3877025
mvg@sint.azm.nl
Inclusion criteria
1. B-CLL confirmed according to WHO Classification;
2. Fludarabine refractory, defined as no response or relapse within 12 months after the last administration of fludarabine monotherapy or fludarabine containing regimen, and needing treatment, or Refractory or relapsed and needing treatment and having deletion of 17p13 or Refractory or relapsed within 24 months after the last administration of fludarabine combined with a monoclonal antibody and needing treatment;
3. Age 18-70 years inclusive;
4. WHO performance status ¡Ü 2;
5. HCT-CI ¡Ü 2;
6. Written informed consent.
Exclusion criteria
1. Intolerance to exogenous protein administration;
2. Previously treated with DHAP;
3. Richter.s transformation;
4. Suspected or documented CNS involvement by CLL;
5. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease);
6. Severe pulmonary dysfunction (CTCAE grade III-IV;
7. Severe neurological or psychiatric disease;
8. Significant hepatic dysfunction (serum bilirubin or transaminases ¡Ý 3 times upper limit of normal) except when caused by leukemic infiltration;
9. Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration);
10. History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
11. Active, uncontrolled infections;
12. Patient known to be HIV-positive;
13. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
14. Pregnant or breast-feeding female patients. Negative pregnancy test at study is mandatory for female patients of childbearing potential.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL1401 |
| NTR-old | NTR1461 |
| Other | EudraCT number 2007-005487-28 : HO88 |
| ISRCTN | ISRCTN wordt niet meer aangevraagd |