Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Behaviors and Mental Disorders

Nervous System Diseases

Rare Diseases

Lymphoma

Aggression

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Lymphosarcoma

All Drugs and Chemicals

Polatuzumab vedotin

Immunoconjugates

Immunologic Factors

Participants will receive study treatment in three phases: Induction Phase, CAR-T Treatment Phase and Consolidation Phase.

During the Induction Phase (Days -42, through -6), participants will receive Mosunetuzumab on Days -42, -35, -28, and -7; and Polatuzumab on Day -28. On Day -6, participants will be evaluated in clinic.

During the CAR-T Treatment Phase (Days -5, through Day 0), participants will receive lymphodepleting chemotherapy for three consecutive days beginning on Day -5, followed by CAR-T Cell therapy via infusion on Day 0.

During the Consolidation Phase (Days +1 through +90), participants will receive Mosunetuzumab on Day +14; and combination Mosunetuzumab and Polatuzumab on Days +35, +56 and +77.

Induction Phase (Days -42 through -7):

* 1 mg of Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -42.
* 2 mg of Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -35.
* 60 mg of Mosunetuzumab administered via intravenous (IV) infusion on (given as per treatment guidelines) on Days -28 and -7.

Consolidation Phase (Day +1 through Day +90): 30 mg IV Mosunetuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Days +14, +35, +56 and +77.

Mosunetuzumab

Induction Phase (Days -42 through -7): 1.8mg/kg of Polatuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Day -28.

Consolidation Phase (Days +1 through +90): 1.8mg/kg of Polatuzumab administered via intravenous (IV) infusion (given as per treatment guidelines) on Days +35, +56 and +77.

Polatuzumab

Participants will receive CAR-T Cell therapy via infusion on Day 0 (given as per treatment guidelines). Prior to CAR-T Cell Therapy, participants will begin receiving lymphodepleting chemotherapy on Days -5 through -3 (given as per treatment guidelines).

CAR-T Cell Therapy

Robby Friedman

Lazaros Lekakis, MD

The purpose of this research study is to test if a combination treatment of chimeric antigen receptor (CAR) T-cell therapy, Mosunetuzumab, and Polatuzumab Vedotin will result in tumor reduction.

CAR-T Cell Therapy, Mosunetuzumab and Polatuzumab for Treatment of Refractory/Relapsed Aggressive Non-Hodgkin's Lymphoma (NHL).

ML43165 - Single Arm Phase 2 Trial of an FDA Approved Anti-CD19 CAR-T Therapy Followed by Mosunetuzumab and Polatuzumab Consolidation for the Treatment of Refractory/Relapsed Aggressive NHL.

Complete Response (CR) rate will be reported as the percentage of participants achieving complete response (CR) to study treatment. Response to therapy will be assessed using Positron Emission Tomography (PET)/ Computerized Tomography (CT) scan following Lugano 2014 criteria (Cheson et al, Journal of Clinical Oncology (JCO), 2014) at 3 months (Day +90) of study treatment. For equivocal PET-CT results, biopsy will be performed after day +90 PET/CT to assess true CR or persistent lymphoma.

Overall response rate (ORR) will be reported as the percentage of participants achieving either complete response (CR) or partial response (ORR = CR + PR) to study treatment. Response to therapy will be assessed using Positron Emission Tomography (PET)/ Computerized Tomography (CT) scan following Lugano 2014 criteria (Cheson et al, Journal of Clinical Oncology (JCO), 2014) up to Day +90 of study treatment.

PFS is defined as the elapsed time from the date of starting treatment to the date of progression, or date of death from any cause; whichever comes first. PFS rate will be reported as the percentage of participants without progressive disease after start of treatment.

Overall survival is defined as the elapsed time from the date of starting treatment to the date of death from any cause. OS rate will be reported as the percentage of participants still alive after start of treatment.

Minimal residual disease (MRD) negativity will be reported as the percentage of participants showing absence of measurable disease in peripheral blood after start of CAR-T Cell therapy. MRD negativity will be assessed by using the Clustering and Alignment of Polymorphic Sequences (CAPSeq) assay.

Duration of response is defined as the elapsed time from date of complete response (CR) to the date of progression or death, whichever is first. DoR will be reported as the percentage of participants who relapsed after achieving CR on the Day +90 PET/CT scan. Relapse rate applies to unequivocal metabolic relapse or/and biopsy confirmed relapse among the patients who achieved CR on day +90 PET-CT

Toxicity rate of CAR-T Cell Therapy will be reported as the percentage of participants with treatment-emergent Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS), after start of therapy, as evaluated by treating physician. The severity of ICANS events in participants will be assessed using American Society for Transplantation and Cellular Therapy (ASTCT) Consensus grading criteria (Lee et al, Biol Blood Marrow Transplant., 2019).

Toxicity rate of CAR-T Cell Therapy will be reported as the percentage of participants with treatment-emergent Cytokine Release Syndrome (CRS) events, after start of therapy, as evaluated by treating physician. The severity of CRS events in participants will be assessed using American Society for Transplantation and Cellular Therapy (ASTCT) Consensus grading criteria (Lee et al, Biol Blood Marrow Transplant., 2019).

Spots Global Cancer Trial Database for CAR-T Cell Therapy, Mosunetuzumab and Polatuzumab for Treatment of Refractory/Relapsed Aggressive Non-Hodgkin's Lymphoma (NHL).

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial