17p-CLL: Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in 17p- Chronic Lymphocytic Leukemia (CLL)

Sponsor

European Society for Blood and Marrow Transplantation (Other)

Overall Status

Completed

CT.gov ID

NCT01675102

Collaborator

European Research Initiative on CLL (Other)

Enrollment

Locations

Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

17p-/p53-mutated chronic lymphocytic leukemia (CLL) is an orphan disease, accounting for approximately 5% of newly diagnosed CLL. This subgroup of patients has a very poor outcome after chemoimmunotherapy. Allogeneic HCT may change the poor prognosis. In a retrospective EBMT-analysis on 44 patients with advanced 17p-CLL 2-year progression-free survival was 45% (95% CI, 30% to 60%) after allogeneic HCT (Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol, 2008, 26, 5094-5100).

Referring to these favorable results and small additional series, patients with 17p-CLL requiring therapy are considered to have an indication for allogeneic transplantation by many CLL study groups. Several CLL study groups recommend allogeneic HCT in 17p-CLL as part of the first- or second line treatment.

The aim is to collect additional evidence on allogeneic HCT in 17p-/p53-mutated CLL in first or second remission by a non-interventional prospective study. Patients shall be registered prior to HCT at the Leiden Office in order to rule out a reporting bias after transplantation.

Condition or Disease	Intervention/Treatment	Phase
CLL

Detailed Description

Objective:

The aim is to determine early PFS after allogeneic HCT in first or second remission of 17p-/p53-mutated CLL within an epidemiologic study.

Methods:

Neither the decision for allogeneic transplantation nor specific treatment recommendations for patients with 17p-/p53-mutated CLL are part of the study. Instead, the study protocol refers to EBMT guidelines. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia 21, 2007, 12-17). Minimal essential data (MED) A and B, defined by the EBMT, will be collected (www.ebmt.org).

The rate of progression-free survival (PFS) at 1 year after HSCT was selected as primary endpoint. Death, clinical relapse or progression but not immune manipulations (taper of immunosuppression, DLI, rituximab) are considered as treatment failure for PFS. Patients without information on one-year follow up will be considered as having experienced treatment failure. The rate of PFS at 1 year will be calculated by dividing the number of patients without treatment failure by the number of patients who met all selection criteria.

For the calculation of the sample size a fixed sample design was selected. The null hypothesis is that the success-rate for PFS is equal or less than 50%. Referring to the retrospective EBMT survey, PFS at one year after allogeneic HCT is expected to be 70%. According to Fleming-A'Hern (1982) the null hypothesis can be rejected with a power of 80% and an alpha error of 5% if a minimum of 24 out of 37 informative patients did not experience treatment failure during the first year after allogeneic HCT (Machin et al, Sample Size Tables for Clinical Studies, Wiley-Blackwell, 3rd edition, 2009). Taking into account a 10% drop-out rate by violation of inclusion criteria the target number of patients to be included was set at 41 patients.

Study Design

Study Type:

Observational

Actual Enrollment :

41 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Allogeneic HSCT in 17p- CLL in First or Second Partial or Complete Remission at Transplant: a Non-interventional Prospective Study.

Study Start Date :

Aug 1, 2010

Actual Primary Completion Date :

Sep 1, 2015

Actual Study Completion Date :

Dec 31, 2015

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) rate [1 year after HSCT]

Secondary Outcome Measures

Rate of MRD-negative complete remissions [1 year after HSCT]
Overall survival, cumulative incidence of relapse and non-relapse mortality [1 year after HSCT]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

17p-/p53-mutated CLL by FISH or sequencing, confirmed by review by an experienced laboratory
first or second partial remission or complete remission at HCT according to the updated NCI-criteria (Hallek 2008)
MRD diagnostic as part of the local standard follow up
allogeneic HCT from a matched related or unrelated donor with up to one mismatch refering to HLA-A, -B, -C and DRB1

Exclusion Criteria:

ex vivo T-cell depletion
in vivo T-cell depletion with alemtuzumab

Contacts and Locations

Locations

	Site	City	Country
1	Rigshospitalitet	Copenhagen	Denmark
2	University Central Hospital	Helsinki	Finland
3	Universitaetsklinikum	Dresden	Germany
4	University Hospital Eppendorf	Hamburg	Germany
5	University of Heidelberg	Heidelberg	Germany
6	Klinik fuer Innere Medzin III	Ulm	Germany
7	Chaim Sheba Medical Centre	Tel-Hashomer	Israel
8	University Hospital	Maastricht	Netherlands
9	University Hospital	Lund	Sweden
10	City Hospital	Nottingham	United Kingdom

Sponsors and Collaborators

European Society for Blood and Marrow Transplantation
European Research Initiative on CLL

Investigators

Principal Investigator: Johannes Schetelig, MD, Medizinische Klinik und Poliklinik I, University Hospital Dresden, Germany
Study Chair: Nicolaus Kroeger, MD, BMT Centre, University Hospital Eppendorf, Hamburg, Germany