Ofatumumab as Part of the Reduced Intensity Conditioning Regimen (RIC) for Patients With High Risk B Non Hodgkin's Lymphoma Undergoing Allogeneic Hematopoietic Cell Transplantation
1. Written informed consent obtained before starting any study-specific procedure
2. Histopathological diagnosis of NHL CD 20 + B cells of different histological
- Lymphoma Diffuse Large Cell B (DLBCL)
- Follicular lymphoma (FL) grade IIIb
- Follicular lymphoma (FL) grade I and II high-risk
- Transformed B-cell lymphoma (LT)
- mantle cell lymphoma (MCL)
- Burkitt lymphoma allogeneic transplant candidate but not myeloablative
3. CD 20 + lymphoma at high risk of having at least one of the following
- Less than a partial remission after two courses of treatment
- relapse after autologous peripheral blood stem cell (PBSCT)
- Evidence of measurable disease (With CT and PET or PET / CT) three months after
- Count inadequate blood stem cells in patients with relapse or partial remission
after two courses of treatment to prevent the execution of a PBSCT.
- patients after first relapse in PR after two courses of treatment in whom the
probability of being progression-free year is very low due to risk factors such
as: first CR of less than 12 months after PBSCT low SLP.
4. Age between 18 and 65 years
5. Performance status (ECOG) < 2
6. Adequate pulmonary function: forced expiratory volume at 1 second > 65% of predicted
or a diffusing capacity of the lung for CO ≥50%.
7. Cardiac ejection fraction greater than 40% measured by scan or echocardiogram.
8. Adequate renal and hepatic system: Creatinine serum < 2 mg/dl, Serum bilirubin
≤1.5mg/dL and alkaline phosphatase ≤ 2.5 x ULN, AST, ALT ≤ 2.5 x ULN ( ≤ 5 x ULN in
case of liver metastasis).
9. Disease status before the transplant should be determined according to Revised
Response Criteria for Malignant Lymphoma [Cheson, 2007],with CT-Scan, PEt or PET/CT
10. To have a family matched or an unrelated 9 or 10/10 matched donor willing to donate
peripheral stem cell
11. Adults with ability to procreate must agree to use effective birth control during
study treatment and at least 6 months later. Provided by adequate contraception, the
hormonal IUD, double barrier method or abstinence.
1. Refractory disease at transplant defined as less than Stable disease after the last
2. Progressive disease at transplant.
3. ECOG ≥ 2 at the time of transplantation
4. More than four chemotherapy lines before transplant
5. HIV-associated lymphoma
6. Positive HIV
7. Presence of human anti-mouse antibody (HAMA) or antichimeric antibody (HACA) levels.
8. 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
9. Participation in another interventional clinical trial
10. 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.
11. Active liver disease or biliary (except Gilbert's disease, cholelithiasis,
12. 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.
13. Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
antiviral treatment such as, but not limited to, chronic renal infection, chronic
chest infection with bronchiectasis, tuberculosis and active Hepatitis C.
14. History of significant cerebrovascular disease in the past 6 months or ongoing event
with active symptoms or sequelae.
15. 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.
16. 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
17. Pregnant or lactating women. Women of childbearing potential must have a negative
pregnancy test at screening.
18. 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.
19. Male subjects unable or unwilling to use adequate contraception methods from study
start to one year after the last dose of protocol therapy.
20. Patients with hypersensitivity to fludarabine, melphalan, tacrolimus, sirolimus and /