What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, particularly those involving monoclonal antibodies like rituximab, ofatumumab, and obinutuzumab, can cause infusion reactions such as fever, chills, rash, and hypotension, especially during the first cycle. Chemotherapy regimens, such as those involving bendamustine, often lead to myelosuppression, resulting in neutropenia, anemia, and thrombocytopenia, along with nausea, vomiting, fatigue, and increased infection risk. Combining these treatments can enhance efficacy but also compound the side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Hodgkin's Lymphoma, including monoclonal antibodies and bispecific antibodies. Rituximab, a monoclonal antibody targeting CD20, was one of the first significant approvals and has been widely used in combination with chemotherapy. More recently, bispecific antibodies like Blinatumomab, which targets CD19 and CD3, have been approved for certain types of NHL. These therapies work by engaging T-cells to target and kill B-cell malignancies. Mosunetuzumab, currently under investigation, similarly targets CD20 and CD3, representing a promising advancement in the treatment landscape for relapsed or refractory aggressive B-cell lymphomas.

What other types of research exist?

Promising novel alternatives to Mosunetuzumab for Non-Hodgkin's Lymphoma patients include: 1) CAR T-cell therapies such as Axicabtagene Ciloleucel and Tisagenlecleucel, which have shown significant efficacy in relapsed or refractory NHL. 2) Bispecific T-cell engagers (BiTEs) like Blinatumomab, which target CD19 and CD3. 3) Antibody-drug conjugates (ADCs) such as Polatuzumab Vedotin, which targets CD79b. 4) Novel BTK inhibitors like Zanubrutinib and Acalabrutinib, which offer improved tolerability and efficacy profiles. These therapies represent cutting-edge advancements in the treatment of NHL and are expected to be significant options in 2024.

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Alkylating agents

Mosunetuzumab + Chemotherapy for B-Cell Lymphoma

Phase 1

Recruiting

Led By Nancy L Bartlett, M.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests adding mosunetuzumab to strong chemotherapy for patients with aggressive B cell lymphoma who haven't responded to other treatments. The drug helps the immune system find and kill cancer cells, aiming to improve treatment before a stem cell transplant. Mosunetuzumab has shown promising results in recent trials.

Who is the study for?

This trial is for adults with certain aggressive B cell lymphomas that have come back or didn't respond to initial treatments. They should be planning an autologous stem cell transplant and must not have had more than two prior chemotherapy lines. Participants need normal blood counts, no major recent surgeries, and can't be pregnant or breastfeeding. Those with autoimmune diseases, a history of severe allergies to monoclonal antibodies, active infections, or liver disease are excluded.

What is being tested?

The study tests mosunetuzumab combined with platinum-based salvage chemotherapy (DHAX or ICE) in patients aiming for stem cell transplantation. It's designed to see if this combination is safe and potentially better than current chemoimmunotherapy options that use rituximab retreatment.

What are the potential side effects?

Mosunetuzumab may cause side effects like infusion reactions (symptoms during or after the drug is given), low blood counts leading to increased infection risk, tiredness, and potential organ inflammation. The exact side effects will vary from person to person.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequencies and grades of treatment-emergent adverse events (TEAEs)

Rate of treatment delay or discontinuation due to treatment-emergent adverse events (TEAEs)

Secondary study objectives

Number of participants with complete response (CR)

Number of participants with partial response (PR)

Number of participants with progressive disease (PD)

+6 more

Side effects data

From 2021 Phase 1 trial • 23 Patients • NCT04313608

41%

Cytokine release syndrome

35%

Diarrhoea

35%

Anaemia

35%

Hypomagnesaemia

35%

Pyrexia

35%

Neuropathy peripheral

24%

Constipation

24%

Platelet count decreased

24%

Neutropenia

24%

Hypophosphataemia

24%

Nausea

24%

Liver function test abnormal

24%

Fatigue

24%

Thrombocytopenia

18%

Lethargy

18%

Hypokalaemia

18%

Arthralgia

18%

Weight decreased

18%

Neutrophil count decreased

18%

Oral candidiasis

18%

Sepsis

18%

Headache

18%

Peripheral sensory neuropathy

12%

Paraesthesia

12%

Vomiting

12%

Superficial vein thrombosis

12%

Rectal haemorrhage

12%

Flushing

12%

Cough

12%

Infusion related reaction

12%

Blood alkaline phosphatase increased

12%

Abdominal pain

12%

Pain in extremity

12%

Gastrooesophageal reflux disease

12%

Alanine aminotransferase increased

12%

Colitis

12%

Abdominal discomfort

12%

Dizziness

Hypocalcaemia

Rash

Performance status decreased

Decreased appetite

Chest pain

Cytomegalovirus infection reactivation

Hyperlipidaemia

Dyspnoea exertional

Vasospasm

Gamma-glutamyltransferase increased

Orthostatic hypotension

Cellulitis

Wound infection

Hypogammaglobulinaemia

Abdominal distension

External ear cellulitis

Tumour lysis syndrome

Upper respiratory tract infection

Back pain

Urinary tract infection

Transient ischaemic attack

Hypertension

Blood creatinine increased

Abdominal tenderness

Seasonal allergy

Injury

Hypoalbuminaemia

Epistaxis

Throat irritation

Hyperglycaemia

Oropharyngeal pain

Intention tremor

Adenocarcinoma

Thrombosis

Rash maculo-papular

Squamous cell carcinoma

Photosensitivity reaction

Depression

Neutropenic sepsis

Vision blurred

Abdominal pain lower

Anal haemorrhage

Aspartate aminotransferase increased

Groin pain

Pain in jaw

100%

80%

60%

40%

20%

Study treatment Arm

Arm A: Glofit-GemOx

Arm B: Mosun-GemOx

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: Mosunetuzumab + ICEExperimental Treatment2 Interventions

* 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.

Group II: Arm A: Mosunetuzumab + DHAXExperimental Treatment2 Interventions

* 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

ICE

2012

Completed Phase 2

~290

Mosunetuzumab

2019

Completed Phase 2

~140

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies, chemotherapy, and targeted therapies. Monoclonal antibodies like rituximab target CD20 on B-cells, leading to their destruction. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cells, including cancerous lymphocytes. Targeted therapies, such as ibrutinib, inhibit specific proteins involved in cancer cell growth and survival. Mosunetuzumab, a bispecific antibody, targets both CD20 on B-cells and CD3 on T-cells, bringing them together to enhance the immune system's ability to kill cancer cells. These mechanisms are crucial for NHL patients as they offer multiple strategies to eliminate cancer cells, potentially improving treatment efficacy and patient outcomes.