Main info

Identifier:

HO88 CLL

Sponsor:

HOVON

Working group party:

Leukemia

Age:

18-70

Stage:

2nd Line

Included patients:

50

(of 50)

Active sites:

19

(of 19)

Title:

Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning for High-risk Relapsed or Refractory CLL.

Timeline

News

Flow

Details

Phase:

Prospective Phase II study

Monitoring Type:

Not any more

Objectives:

Primary objective

• 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.

Secondary objectives

• 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.

Eligibility

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).

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals