PLRG8: Ofatumumab With IVAC Salvage Chemotherapy in Diffuse Large B Cell Lymphoma Patients

Sponsor
Polish Lymphoma Research Group (Other)
Overall Status
Completed
CT.gov ID
NCT01481272
Collaborator
(none)
77
8
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85
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Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
77 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Nov 1, 2011
Actual Primary Completion Date :
Jul 1, 2017
Actual Study Completion Date :
Dec 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: O-IVAC

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

Drug: Ofatumumab
1000 IV, according to detailed instruction included in the protocol, on day 1 of each 21-day cycle, maximum 6 cycles
Other Names:
  • Arzerra
  • Drug: Etoposide
    60mg/m2 IV, daily over 1 hour, on days 1-5 of 21-day cycle, maximum 6 cycles
    Other Names:
  • VePesid
  • 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
    Other Names:
  • Ifex
  • 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
    Other Names:
  • Mesnex
  • 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
    Other Names:
  • Cytosar
  • Drug: Methotrexate
    12mg, it, on day 5 of each 21 days cycle, maximum 6 cycles
    Other Names:
  • Methotrexat Ebeve
  • Drug: Leukovorin
    15mg, po 24 hours after methotrexate it
    Other Names:
  • Folinic Acid
  • 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
    Other Names:
  • Filgrastim
  • Outcome Measures

    Primary Outcome Measures

    1. Response rate [12 months post-therapy]

      Complete response + partial response

    Secondary Outcome Measures

    1. Progression-free survival [12 month post-therapy]

      Staying free of disease progression

    2. Event-free survival [12 month post-therapy]

      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

    3. Overall survival [12 months post-therapy]

      Time since entering the study till death of any reason

    4. Number of participants with adverse events as a measure of safety and tolerability [12 months post-therapy]

      Reporting Adverse Events and Serious Adverse Events

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Dolnośląskie Centrum Transplantacji Komórkowych Wrocław Dolnośląskie Poland 53-439
    2 Instytut Hematologii i Transfuzjologii Warszawa Mazowieckie Poland 02-776
    3 Centrum Onkologii - Istytut im. M.Sklodowskiej-Curie Warszawa Mazowieckie Poland 02-781
    4 Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. ks. Bronisława Markiewicza Brzozów Podkarpackie Poland 16-200
    5 Uniwersyteckie Cenrum Medyczne Gdańsk Pomorskie Poland 80-952
    6 Szpital Morski im. PCK Oddz. Onkologii i Radioterapii Gdynia Pomorskie Poland 81-519
    7 Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach Gliwice Slaskie Poland 44-101
    8 Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Olsztyn Warminsko-Mazurskie Poland 10-228

    Sponsors and Collaborators

    • Polish Lymphoma Research Group

    Investigators

    • Study Chair: Jan Walewski, Prof., CENTRUM ONKOLOGII - INSTYTUT im. Marii Skłodowskiej-Curie ul. W.K. Roentgena 5, 02-781 Warszawa
    • Principal Investigator: 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Polish Lymphoma Research Group
    ClinicalTrials.gov Identifier:
    NCT01481272
    Other Study ID Numbers:
    • PLRG8 (OMB114361)
    • 2010-023568-42
    First Posted:
    Nov 29, 2011
    Last Update Posted:
    Dec 27, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Polish Lymphoma Research Group
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 27, 2021