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Antibodies

Antibodies, Bispecific

Immunoglobulins

Mosunetuzumab is a CD3xCD20 bispecific antibody administered intravenously in the consolidation setting after autologous stem cell transplant (autoSCT). Mosunetuzumab will be given in a step-up dosing schedule beginning on Day 49 after autoSCT on C1D1, C1D8, C1D15, and then Day 1 of all cycles thereafter. Patients will undergo PET-CT restaging around Day 100 post-autoSCT (approximately Cycle 3) and patients in complete response will continue mosunetuzumab for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients not in complete response will discontinue treatment and enter follow-up. All cycles are planned to be 21 days.

Mosunetuzumab is administered intravenously in a "step-up" dosing strategy. The doses will be 1 mg on C1D1, 2 mg on C1D8, 60 mg on C1D15, 60 mg on C2D1, and 30 mg for all doses following.

Mosunetuzumab

Armin Ghobadi, M.D.

Camille Abboud, M.D.

Ramzi Abboud, M.D.

Nancy Bartlett, M.D.

Amanda Cashen, M.D.

Matthew Christopher, M.D., Ph.D.

Zachary Crees, M.D.

John DiPersio, M.D., Ph.D.

Todd Fehniger, M.D., Ph.D.

Brad Kahl, M.D.

Neha Mehta-Shah, M.D.

David Russler-Germain, M.D., Ph.D.

Peter Westervelt, M.D., Ph.D.

Feng Gao, Ph.D.

This phase 1 pilot study examines the feasibility and safety of mosunetuzumab after autologous stem cell transplant for patients with aggressive B cell lymphomas. Mosunetuzumab is an antibody that has been engineered to attach to two target cells in the immune system: T cells that normally perform tasks like killing virus-infected cells, and cancerous B cells. Mosunetuzumab has been designed to direct these T cells to kill the cancerous B cells instead.

Mosunetuzumab Consolidation Therapy After autoSCT in r/r Aggressive B Cell Lymphoma

A Pilot Study Evaluating the Safety and Efficacy of Mosunetuzumab Consolidation Therapy After Autologous Stem Cell Transplantation in Patients With Relapsed/Refractory Aggressive B Cell Lymphoma

Treatment-emergent adverse events (TEAE) are defined as adverse events possibly, probably, or definitely related to mosunetuzumab that occur on or after first dose of study treatment.

Patients are consented and enrolled prior to autoSCT, and given the long delay from consent to treatment, this will allow evaluation of feasibility of this approach.

Progression-free survival (PFS) is defined as the time from day zero of autologous stem cell transplantation to the first occurrence of disease progression as determined by the investigator with use of the Lugano Response Criteria or death from any cause.

Overall survival (OS) is defined as the time from day zero of autologous stem cell transplantation to death from any cause.

Tocilizumab is recommended for treatment of grade 2 CRS and required for grade 3 or 4 CRS. Tocilizumab should be administered by IV infusion for a maximum of 4 doses.

Genentech, Inc.

Washington University School of Medicine

Muromonab-CD3

* 3 cycles (cycle=21 days) of mosunetuzumab with DHAX salvage chemotherapy (selected at the discretion of the treating physician).
* The first 3 patients in each arm will receive Dose Level 1 along with standard dosing of DHAX. The rate of dose-limiting toxicities will determine whether the subsequent 3 patients in each arm are enrolled at Dose Level 1, or alternatively at Dose Level -1.
* For patients tolerating Cycle 1 of treatment, Cycles 2 and 3 will consist of mosunetuzumab administered as a single dose on Day 1 along with DHAX. Patients will undergo PET-CT restaging prior to Cycle 3, and those achieving a CR (or PR, at their physician's discretion) will receive the Cycle 3 dose of mosunetuzumab and DHAX, followed by standard of care stem cell mobilization and autoSCT. Patients with SD or PD after restaging will discontinue study treatment.

* 3 cycles (cycle=21 days) of mosunetuzumab with ICE salvage chemotherapy (selected at the discretion of the treating physician).
* The first 3 patients in each arm will receive Dose Level 1 along with standard dosing of ICE. The rate of dose-limiting toxicities will determine whether the subsequent 3 patients in each arm are enrolled at Dose Level 1, or alternatively at Dose Level -1.
* For patients tolerating Cycle 1 of treatment, Cycles 2 and 3 will consist of mosunetuzumab administered as a single dose on Day 1 along with ICE. Patients will undergo PET-CT restaging prior to Cycle 3, and those achieving a CR (or PR, at their physician's discretion) will receive the Cycle 3 dose of mosunetuzumab and ICE, followed by standard of care stem cell mobilization and autoSCT. Patients with SD or PD after restaging will discontinue study treatment.

-Standard of care. Flexibility in administration is permitted at the discretion of the treating physician.

DHAX

Nancy L Bartlett, M.D.

Fei Wan, Ph.D.

This is a two-arm, open-label, phase Ib single-site study with expansion cohorts testing the addition of mosunetuzumab to intensive platinum-based salvage chemotherapy in patients with relapsed/refractory aggressive B cell lymphoma intending to pursue consolidative autoSCT. The hypothesis of this study is that mosunetuzumab can be safely combined with platinum-based salvage chemotherapy in this patient population, and that this approach may outperform chemoimmunotherapy approaches that instead incorporate rituximab retreatment. The enrolling physician's choice of the chemotherapy backbone will determine a patient's assigned study arm (Arm A = DHAX, Arm B = ICE). The two arms will accrue patients to phase Ib and expansion cohorts as well as be analyzed independently.

Mosunetuzumab in Combination With Platinum-Based Salvage Chemotherapy in Autologous Stem Cell Transplant-Eligible Patients With Relapsed/Refractory Aggressive B Cell Lymphoma

A Phase Ib Study With Expansion Cohorts Evaluating the Safety and Efficacy of Mosunetuzumab in Combination With Platinum-Based Salvage Chemotherapy in Autologous Stem Cell Transplant-Eligible Patients With Relapsed/Refractory Aggressive B Cell Lymphoma

-Treatment-emergent adverse events (TEAE) are defined as adverse events possibly, probably, or definitely related to mosunetuzumab that occur on or after first dose of study treatment.

-As determined by PET-CT after Cycle 2 (PET2) of study treatment per Deauville 5-point scale (Lugano 2014 criteria).

* ORR: Number of participants with complete response (CR) and partial response (PR)
* As determined by PET-CT after Cycle 2 (PET2) of study treatment per Deauville 5-point scale (Lugano 2014 criteria).

-Defined as the time from start of study therapy to the first occurrence of disease progression as determined by the investigator with use of the Lugano Response Criteria or death from any cause.

-Overall survival (OS) is defined as the time from start of study therapy to death from any cause.

Antineoplastic Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Amino Acids

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Acalabrutinib

Rituximab

Vincristine

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

6x R-miniCHOP + 2x Rituximab + Acalabrutinib.

* Rituximab i.v.: 375 mg/m2 (D0)
* Cyclophosphamide i.v.: 400 mg/m² (D1)
* Doxorubicin i.v.: 25 mg/m² (D1)
* Vincristine i.v.: 1 mg (D1)
* Prednisolone p.o.: 40 mg/m² (D1 to D5)
* Acalabrutinib 100 mg p.o. twice daily starting from D1 of first R-miniCHOP cycle continuously to D21 of cycle 8.

Cycles repeated every 3 weeks

R-miniCHOP + Acalabrutinib

* Rituximab i.v.: 375 mg/m2 (D0)
* Cyclophosphamide i.v.: 400 mg/m² (D1)
* Doxorubicin i.v.: 25 mg/m² (D1)
* Vincristine i.v.: 1 mg (D1)
* Prednisolone p.o.: 40 mg/m² (D1 to D5).

Cycles repeated every 3 weeks

R-miniCHOP

Konstantinos Christofyllakis, MD MSc

Manfred Welslau, MD

Börge Arndt, MD

Kristina LErch, MD

Thomas Illmer, MD

Mathias Rummel, Prof MD

Christian Andreas Schmidt, Prof. MD

Franziska Brunner, MD

Martin Bentz, Prof. MD

Kai Wille, MD

Ulf Reinhart, MD

Tobias Gaska, MD

Julian Topaly, MD, PD

Rolf Mahlberg, MD

Heinz Kirchen, MD

Hanno Witte, MD

Andreas Viardot, Prof. MD

Moritz Bewarder, MD, PD

The goal of this clinical trial is to study the addition of Acalabrutinib to standard R-miniCHOP in older adults with DLBCL. The main question it aims to answer is whether progression free survival kann be prolonged with the addition of Acalabrutinib.

Participants will be randomised to receive either R-miniCHOP alone or R-miniCHOP with Acalabrutinib.

Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma

A Randomized, Open-label, Phase 3 Study of Acalabrutinib in Combination With Rituximab and Reduced Dose CHOP (R-miniCHOP) in OldEr Adults With Untreated Diffuse Large B-Cell Lymphoma

PFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Disease progression (PD), relapse after complete remission (CR) or death due to any cause, as per Lugano Classification of 2014. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of disease assessment.

OS, defined by the time between the day of randomization until death due to any cause. Patients who have not experienced an event at the time of analysis will be censored at the date when the patient was last known to be alive.

EFS, defined by the time between the day of randomization until one of the following events occurs, whichever comes first: Progressive disease (PD), relapse after complete remission (CR), initiation of subsequent systemic anti-lymphoma treatment and/or irradiation or death due to any cause, as per Lugano Classification of 2014.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mosunetuzumab Consolidation Therapy After autoSCT in r/r Aggressive B Cell Lymphoma	NCT05412290	B Cell Lymphoma Aggressive Lymp... Diffuse Large B... High-grade B-ce... Transformed Lym... Follicular Lymp...	Mosunetuzumab	18 Years -	Washington University School of Medicine
Mosunetuzumab Consolidation Therapy After autoSCT in r/r Aggressive B Cell Lymphoma	NCT05412290	B Cell Lymphoma Aggressive Lymp... Diffuse Large B... High-grade B-ce... Transformed Lym... Follicular Lymp...	Mosunetuzumab	18 Years -	Washington University School of Medicine
Mosunetuzumab in Combination With Platinum-Based Salvage Chemotherapy in Autologous Stem Cell Transplant-Eligible Patients With Relapsed/Refractory Aggressive B Cell Lymphoma	NCT05464329	Diffuse Large B... High-grade B-ce... Transformed B-C... Follicular Lymp...	Mosunetuzumab DHAX ICE	18 Years -	Washington University School of Medicine
Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma	NCT05820841	Large B-cell Ly... Diffuse Large B...	R-miniCHOP + Ac... R-miniCHOP	61 Years -	Universität des Saarlandes
Mosunetuzumab in Combination With Platinum-Based Salvage Chemotherapy in Autologous Stem Cell Transplant-Eligible Patients With Relapsed/Refractory Aggressive B Cell Lymphoma	NCT05464329	Diffuse Large B... High-grade B-ce... Transformed B-C... Follicular Lymp...	Mosunetuzumab DHAX ICE	18 Years -	Washington University School of Medicine
Acalabrutinib in Combination With R-miniCHOP in Older Adults With Untreated Diffuse Large B-Cell Lymphoma	NCT05820841	Large B-cell Ly... Diffuse Large B...	R-miniCHOP + Ac... R-miniCHOP	61 Years -	Universität des Saarlandes

Spots Global Cancer Trial Database for aggressive b cell lymphoma