Optimizing lymphoDepletion to Improve Outcomes In Patients Receiving Cell Therapy With Yescarta
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Health Network, Toronto
About this trial
This is a Phase 1b study of participants with Diffuse Large B Cell Lymphoma (DLBCL). The purpose of this study is to identify an optimized lymphodenpletion (LD) regimen by evaluating standard and intermediate doses of Fludarabine (Flu) / Cyclophosphamide (Cy) with or without a fixed dose of total lymphoid irradiation (TLI) in the setting of standard of care CAR T cell therapy.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years at the time of informed consent
Life expectancy ≥ 12 weeks
Biopsy-proven and histologically confirmed R/R large B cell lymphoma, including R/R DLBCL, transformation from FL, and R/R PMBCL.
Radiographically documented measurable disease as per Lugano response criteria (i.e. LDi > 1.5 cm that is FDG avid).
Disqualifiers
Persisting disease bulk (defined as ≥10 cm) on restaging imaging following bridging therapy.
History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
History of Richter's transformation of CLL
History of allogeneic stem cell transplant
Trial design
Design model
Sequential
Treatments tested in this trial
Cyclophosphamide
DrugHigher dose than traditional conditioning chemo
TLI
Radiationradiation given with conditioning chemo
Treatment groups
40 Participants
are divided into 4 treatment groupsGroup A: Cyclophosphamide and fludarabine, standard doseNo intervention 0 interventions
Group B: Cyclophosphamide and fludarabine, standard dose with radiationExperimental treatment 2 interventions
Group C: Cyclophosphamide (intermediate dose) and fludarabineExperimental treatment 1 intervention
Group D: Cyclophosphamide (intermediate dose) and fludarabine with radiationExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
safety and tolerability of chemo rads as conditioning chemo
To assess the safety and tolerability of a combination chemo-radiation lymphodepletion (LD) regimen (Fludarabine (Flu)/Cyclophosphamide (Cy) + total lymphoid irradiation (TLI ) in patients receiving standard of care CAR T cell therapy for relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL), by establishing the maximum tolerated doses (MTD) of standard (ZUMA-1) dose Flu/Cy + TLI, and of intermediate dose iCy/Flu +/- TLI, and the dose limiting toxicities (DLT) of standard dose Flu/Cy + TLI, and of intermediate dose iCy/Flu +/- TLI
Time frame
baseline through Day 30Secondary outcomes
1
Overall response rate
The overall response rate is the proportion of patients with either a CR or PR while on study. All patients who do not meet the criteria for objective response by the analysis data cutoff date will be considered non-responders. This will be measured by CT/PET
Time frame
baseline through day 3652
Complete response
To assess the efficacy (complete response (CR) rate at 12 months) of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL. To assess the efficacy of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL. All CR and PR responses may be reviewed by an expert(s) / independent radiologist as required by simultaneous review of patient files and radiologic images
Time frame
baseline through day 3653
Progression free survival
To assess the efficacy (progression free survival (PFS) at 12 months) of a combination chemo-radiation LD regimen (standard dose Flu/Cy + TLI) in patients receiving CAR T cell therapy for R/R DLBCL. To assess the efficacy of an intermediate dose iCy/Flu +/- TLI LD regimen in patients receiving CAR T cell therapy for R/R DLBCL. Progression free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time frame
baseline through day 365Sponsors and contacts
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Source ClinicalTrials.gov