Evaluation of the effect of salvage therapy with R-DHAP followed by reduced-intensity conditioning and allogeneic stem cell transplantation from a sibling or unrelated donor
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
progression-free survival from registration with progression defined as time to:
a. death due to any cause, or
b. 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
B-Cell Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease entity.
Survival from diagnosis varies from several years to more than 25 years. The
most reliable prognostic factors, i.e. cytogenetic abnormalities and previous
antigen-induced activation, only predict in main lines for survival. At the end
a large proportion of patients can not be rescued by currently available
therapies and die of their disease. These patients can be identified because of:
- refractoriness for fludarabine or relapse within 12 months after the last
fludarabine treatment, or
- refractoriness or relapse within two years after combined therapy with
fludarabine and an anti-B-cell antibody, or
- having relapsed in the presence of del 17p13.
Two years progression free survival (PFS) in these patients is 25%.
For these patients allogeneic stem cell transplantation (allo SCT) seems to
improve survival considerably.
From the published series of patients it became clear that a high disease
burden at transplant negatively influences outcome. We therefore aim during
donor search at inducing remission or at least stabilization of the disease
state. It*s of note that the incidence of severe or opportunistic infections in
this phase should be as low as possible to avoid negative influence on the
outcome of allo SCT. The R-DHAP regimen was chosen, to which all participating
are familiar with for treatment of relapsed aggressive non-Hodgkin*s Lymphoma.
The addition of Rituximab is expected to induce higher remission rates
similarly as observed in first and second line treatment of B-CLL, while
toxicity will not increase.
Study objective
Evaluation of the effect of salvage therapy with R-DHAP followed by
reduced-intensity conditioning and allogeneic stem cell transplantation from a
sibling or unrelated donor
Study design
Fase II, prospective, multicenter, non randomized
All patients will be treated with at least three courses of R-DHAP while a
HLA-identical donor is being searched first among siblings and second, if
negative, in the world donor bank. Patients with a donor and responsive or
stable disease (SD) after at least three courses R-DHAP proceed to 'reduced
intensity conditioning' (RIC) alloSCT.
Intervention
All patients will be treated with at least three courses of R-DHAP while a
HLA-identical donor is being searched first among siblings and second, if
negative, in the world donor bank. Patients with a donor and responsive or
stable disease (SD) after at least three courses R-DHAP proceed to 'reduced
intensity conditioning' (RIC) alloSCT.
Study burden and risks
Known side effects of chemotherapy and alloSCT.
R- DHAP may cause tumor lysis in CLL; prophylaxis is strongly recommended and
monitoring during the first week is demanded.
VUMC, 4 noord 138 (PK 5 X 176), De Boelelaan 1117
Amsterdam 1007 MB
NL
VUMC, 4 noord 138 (PK 5 X 176), De Boelelaan 1117
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
- B-CLL confirmed according to WHO Classification
- 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;
- Age 18-70 years inclusive;
- WHO performance status <= 2 (see appendix E);;- HCT-CI <= 2 (see appendix F);
- Written informed consent.
Exclusion criteria
- Intolerance to exogenous protein administration
- Previously treated with DHAP
- Richter*s transformation;
- Suspected or documented CNS involvement by CLL;
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease);
- Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D);
- Severe neurological or psychiatric disease;
- Significant hepatic dysfunction (serum bilirubin or transaminases >= 3 times upper limit of normal) except when caused by leukemic infiltration;
- Significant renal dysfunction (creatinine clearance < 30 ml/min after rehydration);
- History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- Active, uncontrolled infections;
- Patient known to be HIV-positive;
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule;
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2007-005487-28-NL |
| CCMO | NL23247.068.08 |