Study of OFATUMUMAB as Part of the Scheme of Reduced Intensity Conditioning in High Risk Non-Hodgkin Lymphoma B Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Sponsor:
Information provided by (Responsible Party):
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier:
NCT01613300
First received: June 5, 2012
Last updated: NA
Last verified: June 2012
History: No changes posted
  Purpose

The aim of this study is rate of acute graft-versus-host disease II-IV measured at day +365according to conventional criteria (Przepiorka et al. 1995) in patients with high risk non-Hodgkin lymphoma B subjects with Allogeneic Stem Cell Transplant


Condition Intervention Phase
B-Cell Lymphomas
Drug: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea:

Primary Outcome Measures:
  • Rate of acute grade II-IV graft-versus-host disease at 1 year [ Time Frame: 5 years follow-up ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • To analyze the complete response rate after treatment. Further secondary outcomes as described in study summary [ Time Frame: 5 years follow up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 37
Study Start Date: May 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab
Ofatumumab as part of the reduced intensity conditioning regimen (RIC)
Drug: Ofatumumab
Ofatumumab as part of the reduced intensity conditioning regimen (RIC)

Detailed Description:

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 follow-up
  • 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 / L
    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 recorded
  • Safety assessment by the standards of Common Terminology Criteria for adverse events v. 4.0
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 subtypes:

    • 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 conditioning
  3. CD 20 + lymphoma at high risk of having at least one of the following characteristics:

    • 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 PBSCT
    • 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, metastasis)
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01613300

Contacts
Contact: María Dolores Caballero, MD cabarri@usal.es

Locations
Spain
ICO-Hospital Germans Trias i Pujol Not yet recruiting
Badalona, Barcelona, Spain, 08918
Principal Investigator: Christelle Ferrá, MD         
ICO-Hospital Durans i Reynals Not yet recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08907
Principal Investigator: Rafael Duarte, MD         
Hospital Clinic Not yet recruiting
Barcelona, Spain, 08036
Principal Investigator: Carmen Martinez, MD         
Hospital Vall d'Hebron Not yet recruiting
Barcelona, Spain
Principal Investigator: David Valcarcel, MD         
Hospital Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain
Principal Investigator: Javier Briones, MD         
Hospital Reina Sofia Not yet recruiting
Córdoba, Spain
Principal Investigator: Mª. Del Carmen Martín, MD         
H.U. La Paz Not yet recruiting
Madrid, Spain
Principal Investigator: Miguel Ángel Canales, MD         
H.U. 12 de Octubre, Not yet recruiting
Madrid, Spain
Contact: Carlos Grande, MD         
Principal Investigator: Carlos Grande, MD         
H.U. Gregorio Marañón, Not yet recruiting
Madrid, Spain
Contact: Jorge Gayoso, MD         
Principal Investigator: Jorge Gayoso, MD         
H. Morales Meseguer. Not yet recruiting
Murcia, Spain
Contact: Inmaculada Heras, MD         
Principal Investigator: Inmaculada Heras, MD         
Complejo Hospitalario Carlos Haya Not yet recruiting
Málaga, Spain, 29010
Principal Investigator: Mª Jesús Pascual, MD         
Hospital Son Espasses Not yet recruiting
Palma de Mallorca, Spain
Contact: Antonio Gutiérrez, MD       antoniom.gutierrez@ssib.es   
Contact       antoniom.gutierrez@ssib.es   
Principal Investigator: Antonio Gutierrez, MD         
H. Clinico de Salamanca Recruiting
Salamanca, Spain
Contact: Dolores Caballero, MD       cabarri@usal.es   
Principal Investigator: Maria Dolores Caballero, MD         
Hospital Virgen del Rocío Not yet recruiting
Sevilla, Spain, 41013
Principal Investigator: Rocio Parody, MD         
H. La Fe Not yet recruiting
Valencia, Spain
Contact: Isidro Jarque, MD         
Principal Investigator: Isidro Jarque, MD         
Sponsors and Collaborators
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Investigators
Principal Investigator: Maria Dolores Caballero, MD Hospital Clinico de Salamanca
  More Information

No publications provided

Responsible Party: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov Identifier: NCT01613300     History of Changes
Other Study ID Numbers: GELTAMO-O-CRT-2011, 2011-004729-29
Study First Received: June 5, 2012
Last Updated: June 5, 2012
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea:
hodgkin
disease
ofatumumab

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 29, 2014