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

Diffuse Large B Cell Lymphoma Clinical Trial

— PLRG8  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01481272
• Other study ID #: PLRG8 (OMB114361)
• Secondary ID: 2010-023568-42
• Status: Completed
• Phase: Phase 2
• Start date: November 2011
• Est. completion date: December 2018

Study information

• Verified date: December 2021
• Source: Polish Lymphoma Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: December 2018
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Ofatumumab
1000 IV, according to detailed instruction included in the protocol, on day 1 of each 21-day cycle, maximum 6 cycles
• Etoposide
60mg/m2 IV, daily over 1 hour, on days 1-5 of 21-day cycle, maximum 6 cycles
• Ifosfamid
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
• Mesna
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
• Cytarabine
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
• Methotrexate
12mg, it, on day 5 of each 21 days cycle, maximum 6 cycles
• Leukovorin
15mg, po 24 hours after methotrexate it
• Granulocyte-Colony Stimulating Factor
5 microgram/kg or 263 microgram ampoule, sc, daily, starting on day 7 of each 21 day cycle, until ANC>1.0x109/l

Locations

Country	Name	City	State
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. Bronislawa Markiewicza	Brzozów	Podkarpackie
Poland	Uniwersyteckie Cenrum Medyczne	Gdansk	Pomorskie
Poland	Szpital Morski im. PCK Oddz. Onkologii i Radioterapii	Gdynia	Pomorskie
Poland	Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach	Gliwice	Slaskie
Poland	Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie	Olsztyn	Warminsko-Mazurskie
Poland	Centrum Onkologii - Istytut im. M.Sklodowskiej-Curie	Warszawa	Mazowieckie
Poland	Instytut Hematologii i Transfuzjologii	Warszawa	Mazowieckie
Poland	Dolnoslaskie Centrum Transplantacji Komórkowych	Wroclaw	Dolnoslaskie

Sponsors (1)

Lead Sponsor	Collaborator
Polish Lymphoma Research Group

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	Complete response + partial response	12 months post-therapy
Secondary	Progression-free survival	Staying free of disease progression	12 month post-therapy
Secondary	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
Secondary	Overall survival	Time since entering the study till death of any reason	12 months post-therapy
Secondary	Number of participants with adverse events as a measure of safety and tolerability	Reporting Adverse Events and Serious Adverse Events	12 months post-therapy