Ofatumumab as Part of the Reduced Intensity Conditioning Regimen for Patients With High Risk Chronic Lymphocytic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation: a Pilot Study by GETH and GELLC
1. Patients diagnosed with CD20+ chronic lymphocytic leukemia according to the World
2. Patients older than 18 and younger than 70 years old.
3. Patients who failed to meet NCI Working Group criteria for complete or partial
response after therapy with regimens containing fludarabine or with disease relapse
within 12 months after completing therapy with fludarabine containing regimen.
Patients not eligible for fludarabine treatment, could also be included provided the
disease remains unresponsive or relapses with 12 months after completing alternative
salvage regimens (i.e. autologous HCT, bendamustine, gemcitabine, alemtuzumab or
high-dose methyl-prednisolone), OR Patients with novo or acquired "17p deletion"
cytogenetic abnormality. These patients must have received induction chemotherapy but
could be transplanted in first complete or partial response.
4. Patients must have achieved a complete or partial response after the last therapy
given prior to transplantation. Patients with clinically suspected or histologically
confirmed Richter's transformation could be included if they are in complete response
at the time of transplantation.
5. Patients who have not received more than four lines of therapy prior to
6. Patients who have suitable HLA-matched related or unrelated donors willing to receive
G-CSF, undergo apheresis to collect PBMC, and to donate stem cells. Patients with a
single-locus mismatched donor available are also eligible.
7. ECOG functional status of 0 to 2.
8. Life expectancy of at least 6 months.
9. Signed informed consent.
- Intolerance to rituximab or any other anti-CD20 monoclonal antibody.
- Diagnosis of CNS involvement with CLL.
- Prior allogeneic HCT.
- Subjects who have current active hepatic or biliary disease (with exception of
patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
chronic liver disease per investigator assessment).
- Treatment with any known non-marketed drug substance or experimental therapy within 5
terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently
participating in any other interventional clinical study.
- Other past or current malignancy. Subjects who have been free of malignancy for at
least 5 years, or have a history of completely resected non-melanoma skin cancer, or
successfully treated in situ carcinoma are eligible.
- Active infection unresponsive to medical therapy such as, but not limited to, chronic
renal infection, chronic chest infection, tuberculosis and active hepatitis C.
- History of significant cerebrovascular disease in the past 6 months or ongoing event
with active symptoms or sequelae.
- Known HIV positive.
- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within six months prior to randomization, congestive heart failure (NYHA
III-IV), and arrhythmia unless controlled by therapy, with the exception of extra
systoles or minor conduction abnormalities.
- Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
psychiatric disease which in the opinion of the investigator may represent a risk for
- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In
addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB
DNA test will be performed and if positive the subject will be excluded.
- Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which
case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the
- Severe organ dysfunction as defined by: cardiac ejection fraction <40%; DLCO <40%;
calculated GFR < 30 ml/min; or bilirubin > 3 times the upper normal limit (unless due
to CLL or Gilbert syndrome).
- Pregnant or lactating women. Women of childbearing potential must have a negative
pregnancy test at screening.
- Women of childbearing potential, including women whose last menstrual period was less
than one year prior to screening, unable or unwilling to use adequate contraception
from study start to one year after the last dose of protocol therapy. Adequate
contraception is defined as hormonal birth control, intrauterine device, double
barrier method or total abstinence.
- Male subjects unable or unwilling to use adequate contraception methods from study
start to one year after the last dose of protocol therapy.