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

NCT ID: NCT01481272

Last Updated: 2021-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

77 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2018-12-31

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.

Conditions

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Diffuse Large B Cell Lymphoma

Keywords

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Salvage therapy in DLBCL

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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O-IVAC

Ofatumumab Etoposide Ifosfamide Mesna Cytarabine Methotrexate Leukovorin Granulocyte-Colony Stimulating Factor

Group Type EXPERIMENTAL

Ofatumumab

Intervention Type DRUG

1000 IV, according to detailed instruction included in the protocol, on day 1 of each 21-day cycle, maximum 6 cycles

Etoposide

Intervention Type DRUG

60mg/m2 IV, daily over 1 hour, on days 1-5 of 21-day cycle, maximum 6 cycles

Ifosfamid

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

12mg, it, on day 5 of each 21 days cycle, maximum 6 cycles

Leukovorin

Intervention Type DRUG

15mg, po 24 hours after methotrexate it

Granulocyte-Colony Stimulating Factor

Intervention Type DRUG

5 microgram/kg or 263 microgram ampoule, sc, daily, starting on day 7 of each 21 day cycle, until ANC\>1.0x109/l

Interventions

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Ofatumumab

1000 IV, according to detailed instruction included in the protocol, on day 1 of each 21-day cycle, maximum 6 cycles

Intervention Type DRUG

Etoposide

60mg/m2 IV, daily over 1 hour, on days 1-5 of 21-day cycle, maximum 6 cycles

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

Methotrexate

12mg, it, on day 5 of each 21 days cycle, maximum 6 cycles

Intervention Type DRUG

Leukovorin

15mg, po 24 hours after methotrexate it

Intervention Type DRUG

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

Intervention Type DRUG

Other Intervention Names

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Arzerra VePesid Ifex Mesnex Cytosar Methotrexat Ebeve Folinic Acid Filgrastim

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Polish Lymphoma Research Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jan Walewski, Prof.

Role: STUDY_CHAIR

CENTRUM ONKOLOGII - INSTYTUT im. Marii Skłodowskiej-Curie ul. W.K. Roentgena 5, 02-781 Warszawa

Krzysztof Warzocha, Prof.

Role: PRINCIPAL_INVESTIGATOR

Instytut Hematologii i Transfuzjologii, 02-776 Warszawa ul. Indiry Gandhi 14

Andrzej Hellmann, Prof.

Role: PRINCIPAL_INVESTIGATOR

Klinika Hematologii i Tranplantologii, Uniwersyteckie Centrum Medyczne, ul. Dębinki 7, 80-952 Gdańsk

Andrzej Pluta, Prof.

Role: PRINCIPAL_INVESTIGATOR

Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. ks. Bronisława Markiewicza, ul. ks. Bielawskiego 18, 36-200 Brzozów

Andrzej Lange, Prof.

Role: PRINCIPAL_INVESTIGATOR

Dolnośląskie Centrum Transplantacji Komórkowych, 53-439 Wrocław, ul. Grabiszyńska105

Wanda Knopinska-Posluszny, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie; ul.Wojska Polskiego 37, 10-228 Olsztyn

Sebastian Giebel, Prof.

Role: PRINCIPAL_INVESTIGATOR

Klinika Transplantacji Szpiku i Onkohematologii, Centrum Onkologii Instytut im. M. Sklodowskiej-Curie w Gliwicach; al. Wybrzeże Armii Krajowej 15, 44-101 Gliwice

Jan M Zaucha, Prof.

Role: PRINCIPAL_INVESTIGATOR

Oddz. Onkologii i Radioterapii, Szpital Morski im. PCK; ul. Powstania Styczniowego 1, 81-519 Gdynia

Locations

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Dolnośląskie Centrum Transplantacji Komórkowych

Wroclaw, Lower Silesian Voivodeship, Poland

Site Status

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, Poland

Site Status

Centrum Onkologii - Istytut im. M.Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, Poland

Site Status

Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. ks. Bronisława Markiewicza

Brzozów, Podkarpackie Voivodeship, Poland

Site Status

Uniwersyteckie Cenrum Medyczne

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Szpital Morski im. PCK Oddz. Onkologii i Radioterapii

Gdynia, Pomeranian Voivodeship, Poland

Site Status

Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach

Gliwice, Silesian Voivodeship, Poland

Site Status

Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, Warmian-Masurian Voivodeship, Poland

Site Status

Countries

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Poland

Other Identifiers

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2010-023568-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PLRG8 (OMB114361)

Identifier Type: -

Identifier Source: org_study_id