Intratumor Injection of Anti-Mesothelin Immunotoxin LMB-100 With Ipilimumab in Malignant Mesothelioma

Summary

Background:

Mesothelioma is a type of cancer. It originates in cells that line human body cavities. Most people have advanced disease when they are diagnosed. Researchers want to see if a combination of drugs can help.

Objective:

To find a safe dose of LMB-100 in combination with ipilimumab when LMB-100 is injected into tumors.

Eligibility:

Adults ages 18 and older with malignant pleural or peritoneal mesothelioma, that cannot be cured with surgery and has not responded to standard first-line treatments for mesothelioma.

Design:

Participants will be screened with:

* Tumor biopsy or effusion, if needed
* Medical history
* Physical exam
* Blood and urine tests
* Imaging scans
* Heart and lung function tests
* Pregnancy test, if needed

Some screening tests will be repeated during the study.

Participants will get LMB-100 on Days 1 and 4 for up to 2 cycles. Each cycle lasts 21 days. They will stay in the hospital for about 8 days each time they get LMB-100. It will be injected into their tumor with needles.

Participants will get ipilimumab through a tube that is put in a vein. It will be given on Day 2 of the first 2 cycles and Day 1 of the next 2 cycles.

Participants will be assessed for how well they do daily activities. They will give blood and tissue samples for research.

Participants will have a safety visit 4 to 6 weeks after the last dose of the study drugs. Then they will have scans every 6 weeks until their disease gets worse. If their tumor gets bigger, they will have phone, video, or email follow-ups every 12 weeks.

Participants will be on this study for life....

Conditions

• Mesothelioma

Interventions

BIOLOGICAL

LMB-100

LMB-100 administered into lesion on days 1 and 4 during cycle 1.

DRUG

ipilimumab

Administered intravenously once per cycle up to three 21-day cycles. Administration will occur during cycles 2,3,4.

DRUG

Diphenhydramine

Infusion related reactions precaution: All participants will be premedicated with 25-50 mg Diphenhydramine by mouth (PO) or intravenous (IV) (or alternative antihistamine at adequate dose) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration.

DRUG

Famotidine

Infusion related reactions precaution: All participants will be premedicated with 20 mg Famotidine by mouth (PO) or intravenous (IV) (or alternative histamine H2- receptor antagonists (H2) blocker at adequate dose) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration.

DRUG

Acetaminophen

Infusion related reactions precaution: All participants will be premedicated with 650 mg Acetaminophen by mouth (PO) or intravenous (IV) 30-60 minutes (+ 30 minutes) prior to each LMB-100 administration.

DRUG

Dexamethasone

Additional infusion precaution at infusions of LMB-100 after Cycle 1 Day 1 (as appropriate): Dexamethasone 20 mg by mouth (PO), 6-12 hours prior to LMB-100 administration OR 10mg, intravenous (IV), 30-60 minutes prior to LMB-100 administration OR equivalent dose of another corticosteroid as clinically indicated.

PROCEDURE

Biopsy

As feasible at screening, Cycle 1 Day 1 and 5, Cycle 2, 3, \& 4 Day 1, and Cycle 4 Day 21 (±7 days).

DIAGNOSTIC_TEST

FDG-PET

At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks).

DIAGNOSTIC_TEST

CT CAP

At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks).

DIAGNOSTIC_TEST

MRI

At screening, at the end of cycles 2 \& 4 ± 7 days, Follow-Up Visit (4-6 weeks after end of treatment), and Long-Term Follow-Up (every 6-12 weeks).

DIAGNOSTIC_TEST

ECG

At screening, Cycle 1 Day 1, Cycles 2, 3, \& 4 Day 1 and Follow-Up Visit (4-6 weeks after end of treatment).

DIAGNOSTIC_TEST

Echocardiogram

At screening.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Raffit Hassan, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-06-11

Primary Completion

2021-12-06

Completion

2022-01-12

FDA Drug

Yes

Countries

• United States

Study Locations