Follicular LymphomaPhase 2FLMRDNCT04934930
Adjustment of Chemotherapy Duration in Follicular Lymphoma According to Minimal Residual Disease Status
A Phase 2 study testing Bendamustin and Obinutuzumab in people with Follicular Lymphoma, run by Meir Medical Center at 1 site in Israel.
Trial summary
Follicular lymphoma (FL) is a chronic indolent malignancy, where treatment with 6 cycles of bendamustine obinutuzumab (BO) is highly effective but at a cost of increased adverse events. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma
- What is being tested?
- Bendamustin and Obinutuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteIsrael
- Study dates
- 29 Jan 2020to 1 Aug 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and above.
- FL grade I-IIIa, according to world health organization (WHO) classification, in patients who were not previously treated with chemotherapy, have a high tumor bulk \& an indication for treatment, as defined by the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0-2.
- The presence of a molecular marker in bone marrow or peripheral blood for MRD assessment.
Who cannot join
- FL grade IIIb.
- HIV infection.
- HBsAg positivity.
- Active malignancy other than FL
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Meir medical center
Kfar Saba
Uri Abadi, MD, 972-9-7472786, uri.abadi@clalit.org.il
About this study
Official title: Adjustment of Chemotherapy Duration in Follicular Lymphoma Patients According to Peripheral Blood or Bone Marrow Minimal Residual Disease Status
Follicular lymphoma (FL) is a chronic indolent malignancy, where treatment with 6 cycles of bendamustine obinutuzumab (BO) is highly effective but at a cost of increased adverse events.
Tumor specific DNA can be traced in blood and bone marrow of follicular lymphoma patients even after therapy, and when detected after lymphoma treatment it is referred to as minimal residual disease (MRD).
Read more
MRD elimination after effective lymphoma treatment is a marker for deep response and correlates with prolonged remission.
In this study we aim to omit chemotherapy after 4 cycles of treatment in patients achieving MRD elimination after 3 months of therapy, as well as complete metabolic response on positron emission computed tomography (PET-CT), hoping to preserve treatment effectiveness while reducing adverse events.
Read the detailed description
Follicular lymphoma (FL) is the second most common type of non-Hodgkin's lymphoma, with an estimated incidence of 3.18 cases per 100000 people a year in the United States The disease is characterized by an indolent behavior, where often treatment is unnecessary at diagnosis, and a "watch \& wait" approach is the standard of care for asymptomatic patients. FL is also a highly responsive disease for immuno-chemotherapeutic combinations, although most patients will eventually relapse. Since the disease is incurable \& indolent in nature, the therapeutic strategy should aim for disease control, while using treatments with high safety profile in order to minimize the chance for life threatening adverse events.
Therapy with rituximab cyclophosphamide, doxorubicin, vincristine \& prednisone (R-CHOP) combination \& subsequent rituximab maintenance therapy for 24 months shows excellent results with a median progression free survival (PFS) of above a decade.
The more recent GALLIUM trial has shown that combining the monoclonal antibody obinutuzumab with chemotherapy is even more efficacious compared to rituximab combinations. When different combinations were examined in this trial the best results were achieved with the bendamustine-obinutuzumab (BO) combination with 3 year PFS of 84%. Unfortunately the trial also revealed a downside for this effective combination with higher rate of fatal adverse events among patients receiving 6 cycles of bendamustine combinations.
In patients with acute leukemia evaluation for minimal residual disease (MRD) is a routine procedure, and the nature \& length of treatment are guided by MRD status at different time points during therapy.
Among FL patients treated with obinutuzumab-chemotherapy combinations, it has been shown that after 3 cycles of treatment about 90% of patients were MRD negative. In addition MRD negativity at the end of induction in either peripheral blood or bone marrow was found to be associated with improved outcomes in patients with 1st line treatment for FL as well as in the relapsed setting.
These findings raise the possibility for an MRD based treatment approach, where the duration of chemotherapy could be guided by MRD status at mid-induction. Eliminating chemotherapy while continuing immunotherapy after achievement of MRD negativity \& complete metabolic remission on PET-CT at mid-induction could reduce treatment toxicity, while potentially preserving efficacy.
- Conditions
- Follicular Lymphoma
- Being tested
- Bendamustin, Obinutuzumab
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustinDrug
Also called Ribomustin
Chemotherapy
ObinutuzumabDrug
Also called Gazyva
Immunotherapy
| Study group | Role | What they receive |
|---|---|---|
| Reduced number of bendamustine cycles in patients with mid-induction MRD negativity | Experimental | Patients with follicular lymphoma treated with obinutuzumab bendamustine \& achieving MRD negativity as well as complete metabolic response on PET-CT at mid-induction would continue obinutuzumab treatment while omitting bendamustin after 4 cycles. Receives: Drug: Bendamustin; Drug: Obinutuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
Progression-free survival is defined as the time from randomization to the earliest event of progression, relapse, or death from any cause. progression-free survival, is assessed by the investigator.
Measured: Progression free survival will be assessed 24 months after the end of induction.
Secondary outcomes (4)
Progression of disease within 24 months (POD24)
POD24 is defined as disease progression or death due to disease progression occurring within 24 months after treatment initiation, as assessed by the investigator.
Measured: POD24 will be assessed at 24 months after treatment initiation
Overall survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
Overall survival is defined as the time from study initiation to death from any cause.
Measured: Overall survival will be assessed 24 months after the end of induction.
The rate of MRD negativity persistence at 12 months among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
MRD will be assessed at mid-induction, end of induction and subsequently every 6 months.
Measured: Persistence of MRD negativity will be assessed 12 months after study initiation.
The proportion of adverse events among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
The proportion of various adverse events will be assessed as documented by the investigator.
Measured: The proportion of various adverse events will be assessed until 24 months from the end of induction.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2021
- Study start29 Jan 2020
- Primary completion1 Aug 2025 (estimated)
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective multicenter, single arm, phase II study
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Meir Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rabin Medical Center, Tel-Aviv Sourasky Medical Center, Assuta Ashdod Hospital, Ziv Medical Center
- Responsible party
- Sponsor
- Investigators
- Uri Abadi, MD, Principal investigator, Meir Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04934930
- Sponsor's protocol ID
- MMC-19-0209
- Acronym
- FLMRD
- Status last verified
- Jun 2021
- First submitted
- 8 Apr 2021
- Last updated
- 22 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjustment of Chemotherapy Duration in Follicular Lymphoma Patients According to Peripheral Blood or Bone Marrow Minimal Residual Disease Status
- ClinicalTrials.gov ID
- NCT04934930
- Acronym / sponsor ID
- FLMRD / MMC-19-0209
- Conditions
- Follicular Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Meir Medical CenterUniversity, hospital or other
- Collaborators
- Rabin Medical Center, Tel-Aviv Sourasky Medical Center, Assuta Ashdod Hospital, Ziv Medical Center
- Study start
- 29 Jan 2020 (actual)
- Primary completion
- 1 Aug 2025 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 22 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Follicular lymphoma (FL) is a chronic indolent malignancy, where treatment with 6 cycles of bendamustine obinutuzumab (BO) is highly effective but at a cost of increased adverse events.
Tumor specific DNA can be traced in blood and bone marrow of follicular lymphoma patients even after therapy, and when detected after lymphoma treatment it is referred to as minimal residual disease (MRD).
MRD elimination after effective lymphoma treatment is a marker for deep response and correlates with prolonged remission.
In this study we aim to omit chemotherapy after 4 cycles of treatment in patients achieving MRD elimination after 3 months of therapy, as well as complete metabolic response on positron emission computed tomography (PET-CT), hoping to preserve treatment effectiveness while reducing adverse events.
Detailed description
Follicular lymphoma (FL) is the second most common type of non-Hodgkin's lymphoma, with an estimated incidence of 3.18 cases per 100000 people a year in the United States The disease is characterized by an indolent behavior, where often treatment is unnecessary at diagnosis, and a "watch \& wait" approach is the standard of care for asymptomatic patients. FL is also a highly responsive disease for immuno-chemotherapeutic combinations, although most patients will eventually relapse. Since the disease is incurable \& indolent in nature, the therapeutic strategy should aim for disease control, while using treatments with high safety profile in order to minimize the chance for life threatening adverse events.
Therapy with rituximab cyclophosphamide, doxorubicin, vincristine \& prednisone (R-CHOP) combination \& subsequent rituximab maintenance therapy for 24 months shows excellent results with a median progression free survival (PFS) of above a decade.
The more recent GALLIUM trial has shown that combining the monoclonal antibody obinutuzumab with chemotherapy is even more efficacious compared to rituximab combinations. When different combinations were examined in this trial the best results were achieved with the bendamustine-obinutuzumab (BO) combination with 3 year PFS of 84%. Unfortunately the trial also revealed a downside for this effective combination with higher rate of fatal adverse events among patients receiving 6 cycles of bendamustine combinations.
In patients with acute leukemia evaluation for minimal residual disease (MRD) is a routine procedure, and the nature \& length of treatment are guided by MRD status at different time points during therapy.
Among FL patients treated with obinutuzumab-chemotherapy combinations, it has been shown that after 3 cycles of treatment about 90% of patients were MRD negative. In addition MRD negativity at the end of induction in either peripheral blood or bone marrow was found to be associated with improved outcomes in patients with 1st line treatment for FL as well as in the relapsed setting.
These findings raise the possibility for an MRD based treatment approach, where the duration of chemotherapy could be guided by MRD status at mid-induction. Eliminating chemotherapy while continuing immunotherapy after achievement of MRD negativity \& complete metabolic remission on PET-CT at mid-induction could reduce treatment toxicity, while potentially preserving efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective multicenter, single arm, phase II study
| Arm | Type | Receives |
|---|---|---|
| Reduced number of bendamustine cycles in patients with mid-induction MRD negativity | Experimental | Drug: Bendamustin, Drug: ObinutuzumabPatients with follicular lymphoma treated with obinutuzumab bendamustine \& achieving MRD negativity as well as complete metabolic response on PET-CT at mid-induction would continue obinutuzumab treatment while omitting bendamustin after 4 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 and above.
- FL grade I-IIIa, according to world health organization (WHO) classification, in patients who were not previously treated with chemotherapy, have a high tumor bulk \& an indication for treatment, as defined by the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0-2.
- The presence of a molecular marker in bone marrow or peripheral blood for MRD assessment.
Key exclusion criteria (5 listed)
- FL grade IIIb.
- HIV infection.
- HBsAg positivity.
- Active malignancy other than FL
- Pregnancy or lactation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BendamustinAlso: RibomustinChemotherapy | Drug | Reduced number of bendamustine cycles in patients with mid-induction MRD negativity |
| ObinutuzumabAlso: GazyvaImmunotherapy | Drug | Reduced number of bendamustine cycles in patients with mid-induction MRD negativity |
Primary outcome
Progression free survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
Time frame: Progression free survival will be assessed 24 months after the end of induction.
Progression-free survival is defined as the time from randomization to the earliest event of progression, relapse, or death from any cause. progression-free survival, is assessed by the investigator.
4 secondary outcomes
Progression of disease within 24 months (POD24)
Time frame: POD24 will be assessed at 24 months after treatment initiation
Overall survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
Time frame: Overall survival will be assessed 24 months after the end of induction.
The rate of MRD negativity persistence at 12 months among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
Time frame: Persistence of MRD negativity will be assessed 12 months after study initiation.
The proportion of adverse events among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab.
Time frame: The proportion of various adverse events will be assessed until 24 months from the end of induction.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Uri Abadi, MD principal investigator
Meir Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bendamustin and Obinutuzumab in people with Follicular Lymphoma, run by Meir Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Uri Abadi, MD (972-9-7472786, uri.abadi@clalit.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival among patients treated with 4 cycles of BO & 2 additional cycles of obinutuzumab. (time frame: Progression free survival will be assessed 24 months after the end of induction.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021; AzTrials last refreshed its copy on 8 Nov 2026.