Clinical Trial: NCT04934930 - My Cancer Genome

NCT04934930

Description:

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.

Related Conditions:

Grade 1 Follicular Lymphoma
Grade 2 Follicular Lymphoma
Grade 3 Follicular Lymphoma

Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT04934930

Trial Eligibility

Document

Title

Brief Title: Adjustment of Chemotherapy Duration in Follicular Lymphoma According to Minimal Residual Disease Status
Official Title: Adjustment of Chemotherapy Duration in Follicular Lymphoma Patients According to Peripheral Blood or Bone Marrow Minimal Residual Disease Status

Clinical Trial IDs

ORG STUDY ID: MMC-19-0209
NCT ID: NCT04934930

Conditions

Follicular Lymphoma

Interventions

Drug	Synonyms	Arms
Bendamustin	Ribomustin	Reduced number of bendamustine cycles in patients with mid-induction MRD negativity
Obinutuzumab	Gazyva	Reduced number of bendamustine cycles in patients with mid-induction MRD negativity

Purpose

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.

Trial Arms

Name	Type	Description	Interventions
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.	Bendamustin Obinutuzumab

Eligibility Criteria

        Inclusion Criteria:

          1. Age 18 and above.

          2. 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.

          3. Eastern Cooperative Oncology Group (ECOG) performance status grade 0-2.

          4. The presence of a molecular marker in bone marrow or peripheral blood for MRD
             assessment.

        Exclusion Criteria:

          1. FL grade IIIb.

          2. HIV infection.

          3. HBsAg positivity.

          4. Active malignancy other than FL

          5. Pregnancy or lactation.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

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.
Safety Issue:
Description:	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.

Secondary Outcome Measures

Measure:	Progression of disease within 24 months (POD24)
Time Frame:	POD24 will be assessed at 24 months after treatment initiation
Safety Issue:
Description:	POD24 is defined as disease progression or death due to disease progression occurring within 24 months after treatment initiation, as assessed by the investigator.

Measure:	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.
Safety Issue:
Description:	Overall survival is defined as the time from study initiation to death from any cause.

Measure:	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.
Safety Issue:
Description:	MRD will be assessed at mid-induction, end of induction and subsequently every 6 months.

Measure:	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.
Safety Issue:
Description:	The proportion of various adverse events will be assessed as documented by the investigator.

Details

Phase:	Phase 2
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Meir Medical Center

Last Updated

June 22, 2021

Clinical Trials /

Adjustment of Chemotherapy Duration in Follicular Lymphoma According to Minimal Residual Disease Status