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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Polish Lymphoma Research Group
Sponsor:
Information provided by (Responsible Party):
Polish Lymphoma Research Group
ClinicalTrials.gov Identifier:
NCT01481272
First received: November 14, 2011
Last updated: January 27, 2014
Last verified: June 2012
  Purpose

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 Intervention Phase
Diffuse Large B Cell Lymphoma
Drug: Ofatumumab
Drug: Etoposide
Drug: Ifosfamid
Drug: Mesna
Drug: Cytarabine
Drug: Methotrexate
Drug: Leukovorin
Drug: G-CSF
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Polish Lymphoma Research Group:

Primary Outcome Measures:
  • Response rate [ Time Frame: 12 months post-therapy ] [ Designated as safety issue: No ]
    Complete response + partial response


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 12 month post-therapy ] [ Designated as safety issue: No ]
    Staying free of disease progression

  • Event-free survival [ Time Frame: 12 month post-therapy ] [ Designated as safety issue: No ]
    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

  • Overall survival [ Time Frame: 12 months post-therapy ] [ Designated as safety issue: No ]
    Time since entering the study till death of any reason

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 12 months post-therapy ] [ Designated as safety issue: Yes ]
    Reporting Adverse Events and Serious Adverse Events


Estimated Enrollment: 77
Study Start Date: November 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ofatumumab
Ofatumumab, 1000 mg i.v., every 21 days, max. 6 cycles
Drug: Ofatumumab
1000 IV, according to detailed instruction included in the protocol, on day 1 of each 21-day cycle, maximum 6 cycles
Other Name: Arzerra
Drug: Etoposide
60mg/m2 IV, daily over 1 hour, on days 1-5 of 21-day cycle, maximum 6 cycles
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
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
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
Drug: Methotrexate
12mg, it, on day 5 of each 21 days cycle, maximum 6 cycles
Drug: Leukovorin
15mg, po 24 hours after methotrexate it
Drug: G-CSF
5 microgram/kg or 263 microgram ampoule, sc, daily, starting on day 7 of each 21 day cycle, until ANC>1.0x109/l

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01481272

Contacts
Contact: Jan Walewski, Prof. +48 22 546 3248 walewski@coi.waw.pl

Locations
Poland
Dolnośląskie Centrum Transplantacji Komórkowych Recruiting
Wrocław, Dolnośląskie, Poland, 53-439
Contact: Andrzej Lange, Prof.    +48 717831375      
Contact: Monika Mordak, MD PhD    +48 791264657      
Principal Investigator: Andrzej Lange, Prof.         
Sub-Investigator: Monika Mordak, MD PhD         
Centrum Onkologii - Istytut im. M.Sklodowskiej-Curie Recruiting
Warszawa, Mazowieckie, Poland, 02-781
Contact: Ewa Paszkiewicz-Kozik, MD PhD    +4822 546 3222    epaszkiewicz@coi.waw.pl   
Principal Investigator: Jan Walewski, Prof.         
Sub-Investigator: Ewa Paszkiewicz-Kozik, MD PhD         
Sub-Investigator: Joanna Romejko-Jarosinska, MD PhD         
Instytut Hematologii i Transfuzjologii Recruiting
Warszawa, Mazowieckie, Poland, 02-776
Contact: Monika Chelstowska, MD PhD    +48 22 349 61 00      
Principal Investigator: Krzysztof Warzocha, Prof.         
Sub-Investigator: Tomasz Szpila, MD PhD         
Sub-Investigator: Monika Chelstowska, MD PhD         
Sub-Investigator: Malgorzata Jarzembowska, MD         
Szpital Specjalistyczny w Brzozowie Podkarpacki Ośrodek Onkologiczny im. ks. Bronisława Markiewicza Recruiting
Brzozów, Podkarpackie, Poland, 16-200
Contact: Andrzej Pluta, Prof.    +48 134309728    plutaand@gmail.com   
Contact: Beata Kumiega, MD PhD    +48 660443750      
Principal Investigator: Andrzej Pluta, Prof.         
Sub-Investigator: Beata Kumiega, MD PhD         
Uniwersyteckie Cenrum Medyczne Recruiting
Gdańsk, Pomorskie, Poland, 80-952
Contact: Michał Taszner, MD    +48 58 349 2230    mtaszner@uck.gda.pl   
Principal Investigator: Andrzej Hellmann, Prof.         
Sub-Investigator: Michal Taszner, MD PhD         
Klinika Transplantacji Szpiku i Onkohematologii; Centrum Onkologii Instytut im. M.Sklodowskiej-Curie, Oddz. w Gliwicach Not yet recruiting
Gliwice, Slaskie, Poland, 44-101
Contact: Jacek Najda, MD PhD    +48 501315101      
Contact: Malgorzata Sobczyk-Kruszelnicka, MD         
Principal Investigator: Sebastian Giebel Giebel, Prof.         
Sub-Investigator: Jacek Najda, MD PhD         
Sub-Investigator: Malgorzata Sobczyk-Kruszelnicka, MD         
Oddz. Hematologii, Samodzielny Publiczny ZOZ MSW z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Recruiting
Olsztyn, Warminsko-Mazurskie, Poland, 10-228
Contact: Wanda Knopinska-Posluszny, MD PhD    +48 605042390      
Principal Investigator: Wanda Knopinska-Posluszny, MD PhD         
Sub-Investigator: Waldemar Kulikowski, MD         
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
  More Information

No publications provided

Responsible Party: Polish Lymphoma Research Group
ClinicalTrials.gov Identifier: NCT01481272     History of Changes
Other Study ID Numbers: PLRG8 (OMB114361), 2010-023568-42
Study First Received: November 14, 2011
Last Updated: January 27, 2014
Health Authority: Poland: Ministry of Health

Keywords provided by Polish Lymphoma Research Group:
Salvage therapy in DLBCL

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Methotrexate
Etoposide
Leucovorin
Levoleucovorin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on July 22, 2014