Allogeneic hematopoietic cell transplantation in 17p-CLL in first or second complete or partial remission

A non-interventional prospective study of the EBMT and ERIC

Background

The outcome of patients with a del(17) or TP53-mutation in the context of chemotherapy or antibody therapy is detrimental. Although alemtuzumab is a valid treatment option for this subgroup of patients even with this treatment time to relapse is short. In contrast, data from retrospective analyses suggest that a considerable proportion of patients may achieve long-term disease control after allogeneic transplantation (3-year progression-free survival 37% (95% CI, 22% to 52%). Based on data from 13 prospectively studied patients the German CLL3X study reported 4 year progression-free survival of 45% (95%, 17% to 73%). As a consequence 17p-CLL requiring therapy is accepted as an indication for allogeneic transplantation.

Furthermore, several study groups recommend allogeneic hematopoietic cell transplantation (HCT) in 17p-CLL as part of the first-line treatment. The formal level of evidence of this recommendation is low. Randomized controlled studies in this rare indication are not in view or will not be powered to assess the role of allogeneic HCT in this subgroup of patients. Counselling of patients with 17p-CLL, therefore, is difficult – especially in first or second remission.

Goal

The aim is to determine progression-free survival (PFS) after allogeneic HCT in first or second partial or complete remission of 17p-/p53-mutated CLL. Informative data on 41 patients will be collected to top a futility benchmark of 50% one-year PFS with a type I error of 5% and a power of 80%. The study started in May 2010.

Participants

All transplant centers registered within the EBMT may participate.

Approach

The study is a non-interventional study. Therefore, a study treatment or special recommendations for the transplantation procedure cannot be defined. The transplantation should be performed according to current standard treatment options.
The formal process of participation requires registration of the transplant center prior to the first patient. Afterwards, subsequent patients can be registered at the central office in Leiden if they meet selection criteria.

Inclusion criteria

  1. age <70 years
  2. 17p-/p53-mutated CLL by FISH or sequencing, confirmed by review by an experienced laboratory
  3. first or second partial remission or complete remission at HCT according to the updated NCI-criteria
  4. MRD diagnostic as part of the local standard follow up
  5. allogeneic HCT from a matched related or unrelated donor with up to one mismatch referring to HLA-A, -B, -C and DRB1

Exclusion criteria

  1. ex vivo T-cell depletion of the graft
  2. in vivo T-cell depletion with alemtuzumab

Regular MED A and restricted MED B information will be collected. Special attention will be paid to safeguard high documentation quality.

Time-lines

First patient in: June 2010
Last patient in: June 2013
Final analysis:   June 2014

Project Leader

Johannes Schetelig, MD
University Hospital Carl Gustav Carus, Technical University of Dresden
Medical Departement I
Fetscherstraße 74
01307 Dresden
Germany
E-mail: johannes.schetelig@uniklinikum-dresden.de
Phone: +49 351 458-15604
Fax to e-mail: +49 351 449210-637  

Coordination

Jennifer Hoek
Data office Chronic Leukemia Working Party
Department of Medical Statistics & Bioinformatics
LUMC
PO Box 9600
2300 RC Leiden
The Netherlands
E-mail: clwpebmt@lumc.nl
Phone: +31 715264746
Fax to e-mail: +49 71149008723