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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

Phase 2
18 Years
65 Years
Open (Enrolling)
B-Cell Lymphomas

Thank you

Trial Information

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

In addition to above:

- Rate of progression-free survival (PFS) at 12, 24, 36 and 60 months post-transplant
defined as the time between the infusion of progenitors and the disease progression or
death. Patients alive or in complete remission will be censored at the time of last
follow up

- Transplant-related mortality (TRM) at 12, 24, 36 and 60 months after transplantation,
defined as any death not caused directly by lymphoma (any death caused by complications
related to transplantation).

- Overall survival (OS) defined as the time between infusion of progenitors and the
patient's death from any cause. Alive Patients will be censored at the time of last

- Incidence of chronic graft versus host disease (GVHD) wide at 1 and 5 years according
to conventional criteria (Atkinson et al. 1989) and Filipovich et al. (BBMT, 2005).

- Rate of event-free survival (DFS) defined as time interval between diagnosis of
lymphoma and lymphoma progression or relapse or death if the above does not occur.

- Successful graft implantation: is defined as:

1. º: three consecutive days with absolute neutrophil count greater than 0.5 * 109 /

2. ° thrombocythemia exceeds 20 * 109 / L.

- Reconstitution of the immune system: lymphocyte count populations CD20, CD3, CD4 and
CD8 and immunoglobulinemia serum (days +100, 180, 360, 18 months and 24 months).

- intercurrent infections. All sorts of infections (viral, fungal and bacterial)will be

- Safety assessment by the standards of Common Terminology Criteria for adverse events v.

Inclusion Criteria:

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.

Exclusion Criteria:

1. Refractory disease at transplant defined as less than Stable disease after the last
salvage therapy.

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
the patient.

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 /
or excipient

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of acute grade II-IV graft-versus-host disease at 1 year

Outcome Description:

According to conventional criteria. This endpoint will be descriptively reported. Confidence intervals (95% bounds) will be provided. The rate will be analyzed in all patients enrolled at the clinical trial and that no major violation has been produced.

Outcome Time Frame:

5 years follow-up

Safety Issue:


Principal Investigator

Maria Dolores Caballero, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hospital Clinico de Salamanca


Spain: Spanish Agency of Medicines

Study ID:




Start Date:

May 2012

Completion Date:

June 2017

Related Keywords:

  • B-Cell Lymphomas
  • hodgkin
  • disease
  • ofatumumab
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell