HOVON HO88 CLL
- HO88 CLL
- Working group party:
- 2de lijn
- Included patients:
- Active sites:
Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning for High-risk Relapsed or Refractory CLL.
21 DEC 2012: The study is closed for entry of new patients, because it has reached its target of 50 patients.
04 DEC 2012: Within a few months we expect to include the last patient in the HOVON88. With the current inclusion rate we expect that the study will be closed for entry of new patients in February 2013. In order to prevent the situation where a patient has been informed and invited to participate but cannot be registered anymore because of closure of the study in the time needed for the informed consent, please inform HOVON Data Center (HDC) if you have a patient that will be informed about the HOVON 88 CLL study. These patients will be put on a list. When, after screening, the patient is eligible, HOVON Data Center is to be called to see whether it is still possible to register the patient in study.
You will be informed when the target of 50 patients has been reached and the study will be closed for inclusion of new patients. Until then please inform us if you intend to inform a new patient about the study.
09-08-11: Implementation of protocol amendment (protocol version 28MAY2011) in The Netherlands, Belgium followed at 23-08-11.
10-12-10: Please give antibiotics prophylaxis according to local procedures during R-DHAP therapy. Protocol amendment will follow.
05-06-09: SOP MRD measurement and analysis, LDM + LI meeting presentations added to Other documents.
For the Ho88 CLL study there is no central laboratory involved. MRD by flowcytometry has to be performed by your own laboratory (or collaboration with other hospital). PB or BM samples for future molecular studies have to be preserved in liquid nitrogen at your own laboratory.
- Prospective Phase II study
- Monitoring Type:
- Not any more
- To assess, on an intention-to-treat basis, the efficacy and safety of a treatment protocol including salvage chemoimmunotherapy (R-DHAP) followed, in the absence of progression, by RIC alloSCT from sibling or unrelated donors, in high-risk CLL patients as defined in chapter 8.1.1, as measured by the progression free survival as defined in chapter 14.
- To assess the safety and toxicity of three courses of R-DHAP
- To assess the response to three courses of R-DHAP.
- To assess PFS and OS after alloSCT.
- ¨To asses PFS and OS after maximally 6 R-DHAP in case no alloSCT was performed
- To assess disease status at two years after SCT.
- To assess the incidence and course of MRD in patients with CR
- To assess overall survival from registration.
- To assess the incidence of complete, partial and no engraftment.
- To evaluate the incidence and severity of acute and chronic GVHD, and of other treatment related toxicity;
- To evaluate the response of progressive disease or increasing MRD to lowering of immunosuppression or DLI.
- To assess the time to next treatment excluding MRD triggered lowering of immunosuppression or DLI.
- To assess the prognostic value of risk factors at entry including IgH mutation status and karyotypic abnormalities with respect to PFS.
- To assess the functionality of mutated p53 at entry and at relapse.
- 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;
- Pregnant or breast-feeding female patients. Negative pregnancy test at study is mandatory for female patients of childbearing potential;
- Unwillingness or not capable to use effective means of anticonception (all men and premenopausal women).
Eligible patients should be registered before start of treatment. Patients need to be registered at the HOVON Data Center of the Erasmus MC Rotterdam – location Daniel via the Internet via TOP (Trial Online Process; https://www.hdc.hovon.nl/top) or by phone call: +31.10.7041560 or fax +31.10.7041028 Monday through Friday, from 09:00 to 17:00 CET. A logon to TOP can be
requested at the HOVON Data Center for participants.
The following information will be requested at registration:
- Protocol number
- Institution name
- Name of caller/responsible investigator
- Patient’s initials or code
- Patient’s hospital record number (not obligatory)
- Date of birth
- Date written informed consent
- Eligibility criteria
Ziekenhuizen die deelnemen aan het onderzoek staan benoemd op de HOVON website bij het onderzoek. Het kan zijn dat uw ziekenhuis niet genoemd wordt, maar wel aan het onderzoek deelneemt. Informeer hiernaar bij uw arts.