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Trial record 30 of 314 for:    BENDAMUSTINE

First Line Therapy of Advanced Stage Follicular Lymphoma in Patients Not Eligible for Standard Immunochemotherapy (GABe2016)

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ClinicalTrials.gov Identifier: NCT03492775
Recruitment Status : Recruiting
First Posted : April 10, 2018
Last Update Posted : February 28, 2019
Sponsor:
Collaborators:
Hoffmann-La Roche
Mundipharma Research GmbH & Co KG
Information provided by (Responsible Party):
Prof. Dr. Wolfgang Hiddemann, Ludwig-Maximilians - University of Munich

Brief Summary:
The objective of this study is to test whether a combined OBINUTUZUMAB/bendamustine therapy is superior to single agent OBINUTUZUMAB in medically non-fit, 'compromised' patients in terms of anti-lymphoma activity (primary objective), side effects, and quality of life. For the assessment of the anti-lymphoma activity the "event free survival (EFS)" will be applied as primary endpoint. EFS is defined as the time from the day of randomization to the date of first documented disease progression, death by any cause, or institution of a new anti-lymphoma treatment.

Condition or disease Intervention/treatment Phase
Indolent Non-hodgkin Lymphoma Drug: Obinutuzumab Drug: Bendamustine Phase 3

Detailed Description:

Study design:

This is a randomized, open-label, multicenter phase III trial with a parallel-group design of two groups.

Randomization and Interventions:

Randomization between Obinutuzumab single agent treatment versus Obinutuzumab plus Bendamustine followed by Obinutuzumab

Treatment plans:

Arm A: Obinutuzumab single agent Obinutuzumab flat dose of 1000 mg on Day 1 of each of four 28 -day cycles and on Days 8 and 15 of Cycle 1

If at least 'stable disease':

Obinutuzumab flat dose of 1000 mg at weeks 21, 29, 37 and 45 Arm B: Obinutuzumab plus Bendamustine Obinutuzumab flat dose of 1000 mg on Day 1 of each of four 28 -day cycles and on Days 8 and 15 of Cycle 1 plus Bendamustine 70 mg/m2 iv d1+2 of each of four 28 -day cycles

If at least 'stable disease':

Obinutuzumab flat dose of 1000 mg at weeks 21, 29, 37 and 45

The project attempts to establish an evidence based treatment strategy for medically non-fit advanced stage FL-patients who are not eligible for standard therapeutic immunochemotherapy approaches to improve their long term perspectives.

It will furthermore provide a prospectively generated data set which will link performance in the assessment scores IADL, G8 and CIRS-G to medical fitness as judged by the treating physician. The generated data will allow using geriatric and functional tests to define medical fitness and to provide a more solid basis for future studies.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 470 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Randomized Comparison of Single Agent GA101 Versus GA101 Plus Bendamustine Followed by GA101 in Medically Non-fit Patients
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : January 5, 2027


Arm Intervention/treatment
Active Comparator: Arm A:Obinutuzumab single agent

Obinutuzumab flat dose of 1000 mg on Day 1 of each of four 28 -day cycles and on Days 8 and 15 of Cycle 1

If at least 'stable disease':

Obinutuzumab flat dose of 1000 mg at weeks 21, 29, 37 and 45

Drug: Obinutuzumab
Obinutuzumab (GA 101) is a first-in-class, potent, intravenously administered type II anti-CD 20 antibody that is developed by Roche AG for the treatment of B-cell malignancies.
Other Name: GA 101

Active Comparator: Arm B:Obinutuzumab plus Bendamustine

Obinutuzumab flat dose of 1000 mg on Day 1 of each of four 28 -day cycles and on Days 8 and 15 of Cycle 1 plus Bendamustine 70 mg/m2 iv d1+2 of each of four 28 -day cycles

If at least 'stable disease':

Obinutuzumab flat dose of 1000 mg at weeks 21, 29, 37 and 45

Drug: Obinutuzumab
Obinutuzumab (GA 101) is a first-in-class, potent, intravenously administered type II anti-CD 20 antibody that is developed by Roche AG for the treatment of B-cell malignancies.
Other Name: GA 101

Drug: Bendamustine
Bendamustine belongs formally to the alkylators, but has been shown to have a unique mechanism of action. The dose limiting toxicity of bendamustine is its reversible suppression of bone marrow function with drops in leukocyte and thromobocyte counts.
Other Name: Bendamustine hydrochloride; Ribomustin




Primary Outcome Measures :
  1. EFS [ Time Frame: Through study completion, up to 6.5 years ]
    Event Free Survival measured from the day of randomization to the date of first documented disease progression, death by any cause or institution of new anti-lymphoma treatment after initial therapy with OBINUTUZUMAB single agent versus OBINUTUZUMAB plus bendamustine both followed by OBINUTUZUMAB consolidation.


Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: week 19-21 ]
    Response in accordance with the 2007 Revised Response Criteria for Malignant Lymphoma will be assessed after the initial treatment phase.

  2. CR30 [ Time Frame: 30 months after randomization ]
    Rate of patients who has a complete response (CR) at 30 months after randomization

  3. TTF [ Time Frame: Through study completion, up to 6.5 years ]
    The time to treatment failure will be measured from the day of randomization to the date of failure of initial treatment (no response) or first documented disease progression or death by any cause.

  4. PFS [ Time Frame: Through study completion, up to 6.5 years ]
    progression-free survival will be measured from the day of randomization to the date of first documented disease progression or death by any cause.

  5. RD [ Time Frame: week 19 up to 5,5 years follow up ]
    Duration of remission will be measured for responding patients from the end of initial treatment to the date of first documented disease progression or death by any cause.

  6. Time to next anti-lymphoma treatment [ Time Frame: Through study completion, up to 6.5 years ]
    will be measured from the date of randomization to the date of first documented start of a new chemotherapy, radiotherapy or immunotherapy.

  7. Overall Survival [ Time Frame: Through study completion, up to 6.5 years ]
    will be determined from the date of randomization to the date of death irrespective of cause.

  8. Number of SAEs [ Time Frame: Through study completion, up to 6.5 years ]
    Therapy-related toxicities according to the NCI-CTC-criteria will be compared for both treatment arms during the initial treatment and the consolidation treatment period.

  9. Frequency of Hospitalization [ Time Frame: Through study completion, up to 3 years (per patient) ]
    The days of hospitalisation will be compared for both treatment arms during the initial treatment, the consolidation treatment period and the first two years after the end of consolidation.

  10. Duration of Hospitalization [ Time Frame: Through study completion, up to 3 years (per patient) ]
    The duration of hospitalisation will be compared for both treatment arms during the initial treatment, the consolidation treatment period and the first two years after the end of consolidation.

  11. Supportive Care [ Time Frame: Through study completion, up to 6.5 years ]
    The number of blood transfusions, the application of growth factors and the days of treatment with i.v. antibiotics will be compared for both treatment arms

  12. Incidence of secondary transformation to aggressive lymphoma [ Time Frame: Through study completion, up to 6.5 years ]
    Incidence of secondary transformation to aggressive lymphoma

  13. Number of AEs [ Time Frame: Through study completion, up to 6.5 years ]
    Incidence of secondary malignancies

  14. Number of participants that had completed the therapy regularly (including: Total cumulative dose of obinutuzumab and bendamustine, number of cycles, duration of treatment) [ Time Frame: Through study completion, up to 6.5 years ]
  15. QoL [ Time Frame: Through study completion, up to 6.5 years ]
    Quality of Life Analysis scale measurements using the QLQ-C30 questionnaires are collected over time and will be compared for patients receiving OBINUTUZUMAB single agent versus OBINUTUZUMAB plus bendamustine.

  16. Comorbidity assessment will be performed by using the Instrumental Activities of Daily Living (=IADL) [ Time Frame: Through study completion, up to 6.5 years ]
    With the Instrumental Activities of Daily Living (=IADL) the functional status) will be analysed (=instrument to assess independent living skills) The instrument is most useful for identifying how a person is functioning at the present time and for identifying improvement or deterioration over time. There are 8 domains of function measured with the Lawton IADL scale. Historically, women were scored on all 8 areas of function; men were not scored in the domains of food preparation, housekeeping, laundering. However, current recommendations are to assess all domains for both genders. Persons are scored according to their highest level of functioning in that category. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent).

  17. Comorbidity assessment will be performed by using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) [ Time Frame: Through study completion, up to 6.5 years ]

    This can be used to measure the burden of current and chronic illnesses in the older adult.This scoring system measures the chronic medical illness ("morbidity") burden while taking into consideration the severity of chronic diseases in 14 items representing individual body systems.

    The general rules for severity rating are:

    0→No problem affecting that system.

    1. Current mild problem or past significant problem.
    2. Moderate disability or morbidity and/or requires first line therapy.
    3. Severe problem and/or constant and significant disability and/or hard to control chronic problems.
    4. Extremely severe problem and/or immediate treatment required and/or organ failure and/or severe functional impairment.

  18. Comorbidity assessment will be performed by using the G 8 (=geriatric) 8 screening score [ Time Frame: Through study completion, up to 6.5 years ]
    The G8 screening tool was developed to separate fit older cancer patients who were able to receive standard treatment from those that should undergo a geriatric assessment to guide tailoring of therapy. The assessment includes (instrumental) activities of daily living, cognition, mood, nutritional status, mobility, polypharmacy and social support. G8 is an independent predictor of mortality within the first year after inclusion (hazard ratio 3.93; 95 % confidence interval 1.67-9.22, p < 0.001). The G-8 Score is a screening tool containing 8 questions. The total G-8 score lies between 0 and 17. A higher score indicates a better health status.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • "Medically non-fit" defined by

    o ECOG > 2 or ECOG 0-2 with co-morbidities excluding intensive therapy according to local investigator's discretion

  • Documentation of the CIRS-G, IADL, G8 and ECOG Scores before start of treatment
  • Histologically confirmed follicular lymphoma grade I, II or IIIa with material available for central pathology review
  • Stage III/IV or stage II without the option of curative radiotherapy
  • Age > 18 years
  • No prior therapy
  • Presence of at least one of the following symptoms or conditions requiring initiation of treatment:

    • Bulky disease according to the GELF criteria: nodal or extranodal mass > 7cm in its greater diameter
    • B symptoms (fever, drenching night sweats, or unintentional weight loss of >10% of normal body weight over a period of 6 months or less)
    • Hematopoietic insufficiency (at least one of the following: granulocytopenia <1500 cells/μl, Hb < 10 g/dl, thrombocytopenia <100.000 cells/μl)
    • Compressive syndrome
    • Pleural/peritoneal effusion
    • Symptomatic nodal or extranodal manifestations
  • At least one bi-dimensionally measurable lesion (> 1.5 cm in its largest dimension by CT scan or MRI)
  • Adequate hematologic function (unless abnormalities are related to NHL), defined as follows:

    • hemoglobin ≥ 9.0 g/dl
    • absolute neutrophil count ≥ 1500 /μL
    • platelet count ≥ 75000 /μl
  • Women who are not breast feeding, are using effective contraception, are not pregnant and agree not to become pregnant during participation in the trial and during the 18 months thereafter.
  • Men who agree not to father a child during participation in the trial and during the 18 months thereafter.
  • Written informed consent form

Exclusion Criteria:

"Medically fit" patient with the option for more intensive induction therapy such as R-CHOP

  • Transformation to high-grade lymphoma (secondary to "low-grade" follicular lymphoma)
  • Grade IIIb follicular lymphoma
  • Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis).
  • Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone.
  • Prior (< 3 years) or concomitant malignancies except non-melanoma skin cancer or adequately treated in situ cervical cancer.
  • Major surgery (excluding lymph node biopsy) within 28 days prior to registration.
  • Necessity of rapid cytoreduction
  • Serious underlying medical conditions, which could impair the ability of the patient to tolerate the therapy offered in this trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease).
  • Severe hepatic impairment (serum bilirubin > 3.0 mg/dl)
  • Known sensitivity or allergy to murine products
  • Known hypersensitivity to any of the study drugs
  • Treatment within a clinical lymphoma trial within 30 days prior to trial entry
  • Positive test results for chronic HBV infection (defined as positive HBsAg serology) (mandatory testing) Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody (HBSAb) after vaccination or prior but cured hepatitis B are eligible.
  • Positive test results for hepatitis C (mandatory hepatitis C virus [HCV] antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
  • Known history of HIV seropositive status.
  • Patients with a history of confirmed PML
  • Vaccination with a live vaccine within 28 days prior to registration
  • Prior organ, bone marrow or peripheral blood stem cell transplantation
  • Any other co-existing medical or psychological condition that will preclude participation in the study or compromise the ability to understand its nature,meaning and implications

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03492775


Contacts
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Contact: Anja Baumgartner, Dr. 0049-89-4400-77313 anja.baumgartner@med.uni-muenchen.de
Contact: Michael Unterhalt, Dr. 0049-89-4400-74915 michael.unterhalt@med.uni-muenchen.de

Locations
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Germany
Klinikum der Universität München Recruiting
München, Bavaria, Germany, 81377
Sponsors and Collaborators
Prof. Dr. Wolfgang Hiddemann
Hoffmann-La Roche
Mundipharma Research GmbH & Co KG
Investigators
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Study Chair: Wolfgang Hiddemann, Prof.Dr. Hospital of the University of Munich

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Responsible Party: Prof. Dr. Wolfgang Hiddemann, Prof. Dr. med. Wolfgang Hiddemann, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT03492775     History of Changes
Other Study ID Numbers: 2016-000755-27
First Posted: April 10, 2018    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Dr. Wolfgang Hiddemann, Ludwig-Maximilians - University of Munich:
indolent lymphoma
Obinutuzumab
GA101
Bendamustine
medically non-fit patients
Additional relevant MeSH terms:
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Bendamustine Hydrochloride
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological