A Phase II,Open Label, Single Arm, Multicenter Study Investigating the Efficacy and Safety of Glofitamab When Used as a Bridge to and/or Consolidation Post-transplant for Patients With Relapsed/Refractory B-cell Lymphomas Transformed Low Grade B Cell Lymphoma) Fit and Eligible for ASCT
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 40
- Primary Endpoint
- To evaluate the efficacy of glofitamab when used as a bridge to and/or consolidation post-transplant for patients with relapsed/refractory B-cell lymphomas (DLBCL or transformed low grade B cell lymphoma) fit and eligible for ASCT
Overview
Brief Summary
This is an investigator-initiated, open-label, single-arm, multicenter, Phase II clinical study. The study is designed to evaluate the safety and potential effectiveness of glofitamab in adults with their disease, diffuse large B-cell lymphoma (DLBCL has either not responded to initial treatment or has returned after an initial response and who are eligible and medically fit for autologous stem cell transplantation (ASCT). Autologous stem cell transplantation is a commonly used treatment in this situation and involves high-dose chemotherapy followed by infusion of your own stem cells, which are collected from your blood several weeks before the transplant.
The purpose of this study is to assess glofitamab, which is not part of standard treatment. Glofitamab is a type of antibody designed to attach to both lymphoma cells and certain immune cells called T cells. By bringing these cells together, glofitamab may help activate the immune system so that T cells can better recognize and destroy lymphoma cells. In this study, glofitamab may be used as a "bridge" to transplantation and/or as consolidation treatment after the transplant, depending on how the disease responds to chemotherapy given before the transplant.
In recent years, newer immune-based treatments such as CAR-T cell therapy have shown benefit for patients whose lymphoma does not respond to or returns after chemotherapy. CAR-T therapy involves collecting immune cells, modifying them in a laboratory, and then reinfusing them into the patient. However, access to CAR-T therapy is limited in some regions, including Lebanon, and autologous stem cell transplantation remains an important treatment option
Detailed Description
This is an investigator initiated open label, single arm, multicenter, phase II trial investigating the efficacy and safety of Glofitamab when used as a bridge to and/or consolidation post-transplant for patients with relapsed/refractory B-cell lymphomas (DLBCL or transformed low grade B cell lymphoma) fit and eligible for ASCT.
Primary Objective: To evaluate the efficacy of glofitamab when used as a bridge to and/or consolidation post-transplant for patients with relapsed/refractory B-cell lymphomas (DLBCL or transformed low grade B cell lymphoma) fit and eligible for ASCT ,
Secondary Objectives:
- To evaluate the efficacy of glofitamab when used as a bridge to and/or consolidation post-ASCT.
- To evaluate the safety and tolerability of glofitamab in this setting
- To evaluate the effect of glofitamab when used as a bridge to and/or consolidation post ASCT on health-related quality of life (HRQoL) Exploratory Objectives
- To evaluate the effect of treatment with glofitamab on acute phase reactants such as fibrinogen and its clinical significance.
Adult patients (age 18-65) with primary refractory disease or relapsed CD20-positive DLBCL (all subtypes including primary mediastinal B cell lymphoma, high grade B cell lymphoma, large B cell lymphoma etc) or transformed low grade B-cell lymphoma, who are eligible for ASCT, planned to receive salvage therapy with Rituximab-chemotherapy regimens followed by ASCT.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •\- To be eligible to participate in this trial, an individual must meet all of the following criteria:
- •Provision of signed and dated informed consent form (ICF) ) by the patient/impartial witness/legal representative before any trial related procedures.
- •Male or female aged between 18 and 65 years.
- •Ability and willingness to comply with the study protocol.
- •Histologically confirmed diagnosis of primary refractory or relapsed DLBCL (all subtypes including primary mediastinal B cell lymphoma, high grade B cell lymphoma, large B cell lymphoma etc) or transformed low grade B cell lymphoma planned for salvage Rituximab-chemotherapy regimens followed by ASCT.
- •Patients with a life expectancy of at least 6 months.
- •All patients must be stable without any signs of active infection, systemic (oral or parenteral) corticosteroid or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled non-absorbable and topical corticosteroid use are permitted as indicated.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks.
- •Women of child-bearing potential and male subjects shall agree to take medically acceptable contraception measures while on study treatment and for 3 months following completion of study treatment. All women of child-bearing potential must have a negative blood pregnancy test at screening.
- •Women must remain abstinent or use contraceptive methods with a failure rate of ≤1% per year during the study treatment period and for 2 months after the final dose of glofitamab, 3 months after the final dose of tocilizumab (if applicable), 12 months after rituximab or chemotherapy, or 18 months after the final dose of obinutuzumab. Women must refrain from donating eggs during this same period. A woman is considered of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (i.e., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of ≤1% per year include bilateral tubal ligation, male sterilization, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form. For men who are not surgically sterile (or with azoospermia for other reasons): Investigators will discuss sperm conservation prior to initiation of study treatment for male participants. Participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating sperm, as defined below: With a female partner of childbearing potential who is not pregnant, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of ≤1% per year during the study treatment period and for 2 months after the final dose of glofitamab, 3 months after the final dose of tocilizumab (if applicable), 6 months after rituximab, ICE (ifosfamide, carboplatin, and etoposide) or obinutuzumab. Men must refrain from donating sperm during this same period. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.
Exclusion Criteria
- •An individual, who meets ANY of the following criteria, will be excluded from participation in this trial:
- •Patients receiving any investigational drug, biological, immunological therapy within the previous 21 days before enrollment.
- •Presence of any severe or uncontrolled systemic disease or condition, including serious cardiac, pulmonary or renal conditions; any type of bacterial, viral, fungal or other infection that would pose a significant risk to the patient in the opinion of the investigator; or active Hepatitis B or positive HCV antibodies.
- •Any unresolved toxicities from prior therapy, greater than CTCAE-version 5 grade 2 at the time of starting study treatment, with exception of alopecia.
- •Patients with a significant cardiovascular disease or condition, including any of the following:
- •Congestive heart failure (CHF) currently requiring therapy and patients with New York Heart Association Class III/IV CHF
- •LVEF \< 50%
- •Need for antiarrhythmic medical therapy for a ventricular arrhythmia or patients with uncontrolled or unstable cardiac arrhythmias
- •Severe conduction disturbance (e.g., second- or third-degree AV block)
- •Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
Arms & Interventions
single arm study assessing the efficacy and safety of Glofitamab as a bridge to and/or consolidation
Participants who complete two cycles of Rituximab-chemotherapy will undergo evaluation by PET scan.
- Complete responders will proceed to a third cycle of Rituximab-chemotherapy, followed by autologous stem cell transplantation (ASCT) and six cycles of consolidation Glofitamab.
- Participants with an incomplete response will receive three cycles of salvage Glofitamab, after which they will be re-evaluated by PET scan. Patients achieving a complete response at this stage will proceed to ASCT, followed by three cycles of consolidation Glofitamab. Non-responders will be discontinued from the study
Intervention: Glofitamab (Drug)
Outcomes
Primary Outcomes
To evaluate the efficacy of glofitamab when used as a bridge to and/or consolidation post-transplant for patients with relapsed/refractory B-cell lymphomas (DLBCL or transformed low grade B cell lymphoma) fit and eligible for ASCT
Time Frame: 3 years
Progression free survival (PFS) at 1 year post relapse-defined as the time from infusion of first salvage chemotherapy to the first occurrence of disease progression or death from any cause, whichever occurs first as determined by the investigator
Secondary Outcomes
- To evaluate the 3 years overall survival(3 years)
- To evaluate the safety and tolerability of glofitamab in this setting(3 years)
- To evaluate the effect of glofitamab when used as a bridge to and/or consolidation post ASCT on health-related quality of life (HRQoL)(3 years)
- To evaluate the effect of treatment with glofitamab on acute phase reactants such as fibrinogen and its clinical significance(1 year)
- To Assess the complete response rate(1 year)
- To Assess the rate of ASCT(1 year)
- clinical complete response rate(6 months)
- Rate of ASCT for patients receiving glofitamab as salvage therapy(6 months)