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

NCT01481272 | Completed Phase 2 DMC

• 2 other identifiers: PLRG8 (OMB114361)2010-023568-42
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 8

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).

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Salvage therapy in DLBCL

Outcome Measures

Primary Outcomes (1)

• Response rate

  Complete response + partial response

  12 months post-therapy

Secondary Outcomes (4)

• Progression-free survival

  12 month post-therapy

• Event-free survival

  12 month post-therapy

• Overall survival

  12 months post-therapy

• Number of participants with adverse events as a measure of safety and tolerability

  12 months post-therapy

Study Arms (1)

O-IVAC

EXPERIMENTAL

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

Drug: Ofatumumab; Drug: Etoposide; Drug: Ifosfamid; Drug: Mesna; Drug: Cytarabine; Drug: Methotrexate; Drug: Leukovorin; Drug: Granulocyte-Colony Stimulating Factor

Interventions

Ofatumumab DRUG

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

Also known as: Arzerra

O-IVAC

Etoposide DRUG

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

Also known as: VePesid

O-IVAC

Ifosfamid 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

Also known as: Ifex

O-IVAC

Mesna 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

Also known as: Mesnex

O-IVAC

Cytarabine 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

Also known as: Cytosar

O-IVAC

Methotrexate DRUG

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

Also known as: Methotrexat Ebeve

O-IVAC

Leukovorin DRUG

15mg, po 24 hours after methotrexate it

Also known as: Folinic Acid

O-IVAC

Granulocyte-Colony Stimulating Factor DRUG

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

Also known as: Filgrastim

O-IVAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Polish Lymphoma Research Group: lead

Study Sites (8)

Dolnośląskie Centrum Transplantacji Komórkowych

Wroclaw, Lower Silesian Voivodeship, 53-439, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, 02-776, Poland

Location

Centrum Onkologii - Istytut im. M.Sklodowskiej-Curie

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

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

Brzozów, Podkarpackie Voivodeship, 16-200, Poland

Location

Uniwersyteckie Cenrum Medyczne

Gdansk, Pomeranian Voivodeship, 80-952, Poland

Location

Szpital Morski im. PCK Oddz. Onkologii i Radioterapii

Gdynia, Pomeranian Voivodeship, 81-519, Poland

Location

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

Gliwice, Silesian Voivodeship, 44-101, Poland

Location

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

Olsztyn, Warmian-Masurian Voivodeship, 10-228, Poland

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

ofatumumab; Etoposide; Ifosfamide; Mesna; Cytarabine; Methotrexate; Leucovorin; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Enzymes and Coenzymes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Jan Walewski, Prof.

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

  STUDY CHAIR

• Krzysztof Warzocha, Prof.

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

  PRINCIPAL INVESTIGATOR

• Andrzej Hellmann, Prof.

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

  PRINCIPAL INVESTIGATOR

• Andrzej Pluta, Prof.

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

  PRINCIPAL INVESTIGATOR

• Andrzej Lange, Prof.

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

  PRINCIPAL INVESTIGATOR

• Wanda Knopinska-Posluszny, MD PhD

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

  PRINCIPAL INVESTIGATOR

• Sebastian Giebel, Prof.

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

  PRINCIPAL INVESTIGATOR

• Jan M Zaucha, Prof.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2011
• First Posted: November 29, 2011
• Study Start: November 1, 2011
• Primary Completion: July 1, 2017
• Study Completion: December 1, 2018
• Last Updated: December 27, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (8)