Clinical trial NCT01481272: Ofatumumab With IVAC Salvage Chemotherapy in Diffuse Large B Cell Lymphoma Patients
Official title: A Phase II Trial on Ofatumumab With IVAC Salvage Chemotherapy in Diffuse Large B Cell Lymphoma Patients Progressing or Relapsed After Prior R-CHOP Treatment Not Suitable for Autologous Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: Salvage therapy in DLBCL
Lead sponsor: Polish Lymphoma Research Group
Sponsor class: NETWORK
First posted: 2011-11-29
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: It is expected that addition of anti-CD20 antibody - ofatumumab would enhance the activity of the etoposide+ifosphamide with mesna+cytarabine+methotrexate+lenograstim or filgrastim (IVAC) regimen. This study is planned to determine the efficacy and safety of ofatumumab in combination with IVAC chemotherapy in patients with CD20 positive diffuse large B cell lymphoma progressing or relapsed after prior R-CHOP chemotherapy not suitable for Autologous Stem Cell Transplant (ASCT).

Detailed description: The purpose of this study is to assess the Overall Response Rate (ORR) = Complete Response (CR) + Partial Response (PR) in adult Diffuse Large B Cell Lymphoma (DLBCL) patients progressing or relapsed after prior R-CHOP treatment not suitable for ASCT treated with O-IVAC salvage chemotherapy regimen. The secondary objective is the evaluation of progression-free survival (PFS), event-free survival (EFS), overall survival (OS), safety and tolerability.

Eligibility criteria: Inclusion Criteria:

* Patients under consideration for participation in this study must meet all of the following inclusion criteria:
* Histologically confirmed CD20 positive diffuse large B-cell lymphoma.
* Progressing or relapsed following prior treatment including but not limited to rituximab-CHOP chemotherapy regimen.
* Not suitable for ASCT (age \> 60 years, PS ≥ 2, prior ASCT as a part of the previous treatment for DLBCL, and/or other medical conditions that unable the patients to undergo the ASCT, e.g. NYHA II, creatinine clearance \< 50 mL/min).
* Age ≥ 18 years.
* ECOG/ WHO performance status grades 0 - 3.
* Resolution of toxicities from previous therapy to grade ≤ 1.
* Written signed and dated informed consent prior to any study procedures being performed.

Exclusion Criteria:

* Known or suspected hypersensitivity to study treatments.
* Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
* Screening laboratory values:

  * platelets \< 75 x 109/L (unless due to DLBCL involvement of the bone marrow),
  * neutrophils \< 1.5 x 109/L (unless due to DLBCL involvement of the bone marrow),
  * creatinine \> 2.0 times upper normal limit (unless normal creatinine clearance),
  * total bilirubin \>1.5 times upper normal limit (unless due to DLBCL involvement of liver or a known history of Gilbert's disease),
  * ALT \> 2.5 times upper normal limit (unless due to DLBCL involvement of liver),
  * alkaline phosphatase \> 2.5 times upper normal limit (unless due to DLBCL involvement of the liver or bone marrow).
* 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 enrolment, 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.
* 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.
* History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequel.
* 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 the patient.
* Positive serology for Hepatitis B (HB).
* Positive serology for hepatitis C (HC).
* 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.
* Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
* Patients unwilling or unable to comply with the protocol.

Primary outcomes:
measure: Response rate
timeFrame: 12 months post-therapy
Secondary outcomes:
measure: Progression-free survival
timeFrame: 12 month post-therapy
measure: Event-free survival
timeFrame: 12 month post-therapy
measure: Overall survival
timeFrame: 12 months post-therapy
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: 12 months post-therapy
Other outcomes:
Locations:
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum Transplantacji Komórkowych
state: Dolnośląskie
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Warszawa
country: Poland
facility: Centrum Onkologii - Istytut im. M.Sklodowskiej-Curie
state: Mazowieckie
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. ks. Bronisława Markiewicza
state: Podkarpackie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Cenrum Medyczne
state: Pomorskie
city: Gdynia
country: Poland
facility: Szpital Morski im. PCK Oddz. Onkologii i Radioterapii
state: Pomorskie
city: Gliwice
country: Poland
facility: Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach
state: Slaskie
city: Olsztyn
country: Poland
facility: Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie
state: Warminsko-Mazurskie
Study officials:
affiliation: CENTRUM ONKOLOGII - INSTYTUT im. Marii Skłodowskiej-Curie ul. W.K. Roentgena 5, 02-781 Warszawa
name: Jan Walewski, Prof.
role: STUDY_CHAIR
affiliation: Instytut Hematologii i Transfuzjologii, 02-776 Warszawa ul. Indiry Gandhi 14
name: Krzysztof Warzocha, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinika Hematologii i Tranplantologii, Uniwersyteckie Centrum Medyczne, ul. Dębinki 7, 80-952 Gdańsk
name: Andrzej Hellmann, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. ks. Bronisława Markiewicza, ul. ks. Bielawskiego 18, 36-200 Brzozów
name: Andrzej Pluta, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Dolnośląskie Centrum Transplantacji Komórkowych, 53-439 Wrocław, ul. Grabiszyńska105
name: Andrzej Lange, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie; ul.Wojska Polskiego 37, 10-228 Olsztyn
name: Wanda Knopinska-Posluszny, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinika Transplantacji Szpiku i Onkohematologii, Centrum Onkologii Instytut im. M. Sklodowskiej-Curie w Gliwicach; al. Wybrzeże Armii Krajowej 15, 44-101 Gliwice
name: Sebastian Giebel, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Oddz. Onkologii i Radioterapii, Szpital Morski im. PCK; ul. Powstania Styczniowego 1, 81-519 Gdynia
name: Jan M Zaucha, Prof.
role: PRINCIPAL_INVESTIGATOR
References: