Ofatumumab With IVAC Salvage Chemotherapy in Diffuse Large B Cell Lymphoma Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Drug: Ofatumumab
* Drug: Etoposide
* Drug: Ifosfamid
* Drug: Mesna
* Drug: Cytarabine
* Drug: Methotrexate
* Drug: Leukovorin
* Drug: Granulocyte-Colony Stimulating Factor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: O-IVAC<br>Ofatumumab Etoposide Ifosfamide Mesna Cytarabine Methotrexate Leukovorin Granulocyte-Colony Stimulating Factor | Drug: Ofatumumab<br>* 1000 IV, according to detailed instruction included in the protocol, on day 1 of each 21-day cycle, maximum 6 cycles<br>* Other names: Arzerra;Drug: Etoposide<br>* 60mg/m2 IV, daily over 1 hour, on days 1-5 of 21-day cycle, maximum 6 cycles<br>* Other names: VePesid;Drug: Ifosfamid<br>* 1500mg/m2 or 1000mg/m2 (patients >/=60 years), IV, daily over 1 hour, on 1-5 days of each 21-day cycle, maximum 6 cycles<br>* Other names: Ifex;Drug: Mesna<br>* 300mg/m2 or 200mg/m2 (patients >/=60 years), IV, over 1 hour, mixed with ifosfamid then 900mg/m2 or 600mg/m2 (patients >/=60 years)over 12 hour or by local practice, on 1-5 days of each 21 day cycle, maximum 6 cycles<br>* Other names: Mesnex;Drug: Cytarabine<br>* 2g/m2 or 0,5-1g/m2 (patients >/= 60 years), IV, over 3 hours, 12 hourly (total of 4 doses), on days 1-2 of each 21 day cycle, maximum 6 cycles<br>* Other names: Cytosar;Drug: Methotrexate<br>* 12mg, it, on day 5 of each 21 days cycle, maximum 6 cycles<br>* Other names: Methotrexat Ebeve;Drug: Leukovorin<br>* 15mg, po 24 hours after methotrexate it<br>* Other names: Folinic Acid;Drug: Granulocyte-Colony Stimulating Factor<br>* 5 microgram/kg or 263 microgram ampoule, sc, daily, starting on day 7 of each 21 day cycle, until ANC>1.0x109/l<br>* Other names: Filgrastim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Complete response + partial response | 12 months post-therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Staying free of disease progression | 12 month post-therapy | 
| Event-free survival | Staying free of event such as disease progression, relapse, death, starting new anticancer therapy, patient's refusal to continue study treatment, Serious Adverse Event that causes discontinuation of study treatment | 12 month post-therapy | 
| Overall survival | Time since entering the study till death of any reason | 12 months post-therapy | 
| Number of participants with adverse events as a measure of safety and tolerability | Reporting Adverse Events and Serious Adverse Events | 12 months post-therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Salvage therapy in DLBCL