Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis

February 5, 2025 updated by: Alexion Pharmaceuticals, Inc.

Phase Ia/Ib Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis

The purpose of this study is to examine the tolerance, safety, pharmacokinetics, and possible clinical benefit of the good manufacturing practice (GMP)-grade amyloid fibril-reactive chimeric (Ch) IgG1 mAb 11-1F4 in patients with amyloid light-chain (AL) amyloidosis.

The phase 1a part will involve at least 3 patients and a maximum of 18 patients. The first patient will receive the starting dose of the antibody and, if tolerated, the following patients will each receive (if tolerated) progressively higher doses of the antibody. Patients in part 1a of the trial will receive only one infusion of the drug. Patients treated in the phase 1a part receive lower dosage which might not be effective.

Once the maximal tolerated dosage is established during the phase 1a part, the investigators will accrue patients to the phase 1b part of the trial. Patients will receive 4 infusions, once each week for 4 weeks. Patients who were treated in the part 1a of the trial and showed no toxicity can be also treated in the part 1b of the trial. The first patient will receive the starting dose of the antibody and, if tolerated, the following patients will each receive (if tolerated) progressively higher doses of the antibody. When the investigators reach the maximum tolerated dose without toxicity, the investigators will enroll another 4 patients to receive the same dose. If there are no toxicities, another 4 patients will be treated at the next dose level, and so forth. Patients treated in Phase 1b may receive lower dosages which might not be effective. The goal of Phase 1b is to establish the tolerance and possible beneficial effects of 11-1F4. If successful, treatment with this antibody would represent a novel approach in the care of individuals with AL amyloidosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Presently, treatment of patients with amyloid light chain (AL) amyloidosis is limited to reducing production of the amyloid-forming light-chain protein by giving conventional or high-dose (with stem cell transplant) anti-plasma cell chemotherapy, as used for patients with multiple myeloma. Although this approach has extended survival, the prognosis remains poor due to the persistence or progression of the amyloid deposits in vital organs, such as the heart or kidney. A different treatment strategy would be to attempt to reduce and/or eliminate these deposits. This study evaluates this by administering an anti-amyloid monoclonal antibody, 11-1F4. This compound has been shown to reduce/destroy this material in an experimental animal model of amyloidosis.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have a confirmed diagnosis of AL amyloidosis based on accepted clinical and laboratory criteria.

  • Patients are greater than 21 years old.

    • Female patients are not of child bearing potential or if they are of child bearing potential, they must not be pregnant or breast-feeding.
    • Patients have a life expectancy greater than 3 months.
    • Patients have an Eastern Cooperative Oncology Group (ECOG)-specified performance status of less than or equal to 3.
  • Patients to be included are those with measurable, localized amyloid deposits (larynx, subcutaneous tissue, muscle, lung, lymph nodes) or clinically evident systemic disease (liver, kidney, heart, etc).
  • Only patients with prior systemic therapy with relapsed/refractory disease are eligible, unless they have declined or are not eligible for high-dose melphalan and autologous hematopoietic stem cell transplant (HSCT) or any other standard therapy that has been known to be life-prolonging or life-saving.
  • Patients have adequate organ function.
  • Patients with cancer are eligible provided they meet specific criteria.
  • Patients must provide signed, written, informed consent and be willing and able to comply with eligibility requirements, scheduled, visits, and follow-up studies.

Exclusion Criteria:

  • Non-AL amyloidosis.
  • Renal failure (on dialysis).
  • Females who are pregnant or breast-feeding.
  • ECOG Performance Status greater than 3.
  • Seriously limited cardiac, renal, or hepatic function.
  • Uncontrolled infection or significant co-morbidity (e.g., uncontrolled diabetes, severe diarrhea).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase Ia

Administration of Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4:

A 1-patient cohort will be infused with 0.5 mg/m2 of Ch 11-1F4 and, if tolerated, the doses in the next patients will be increased to 5, 10, 50, 100, 250, and finally, 500 mg/m2. All individuals will be evaluated prior to treatment, after infusion weekly for four weeks, as well as at 8 weeks.
Drug: Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4
The antibody binds to the pathologic material and initiates a neutrophil/macrophage response
Other Names:
  • Ch mAb 11-1F4
Experimental: Phase Ib

Administration of Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4:

Subjects will receive four weekly infusions of the monoclonal anti-body at Dose Level 1 (0.5 mg/m2). If tolerated, the doses in the next patients will be increased to 5, 10, 50, 100, 250, and finally, 500 mg/m2. When the highest tolerated dose is reached without toxicity in 2 patients, an additional 4 patients will be enrolled and infused at that dose. Escalation or de-escalation will continue until we have determined the highest dose level at which less than 2 patients experience toxicity. All individuals will be evaluated prior to each course of treatment, as well as at weeks 5, 8, and 12.
Drug: Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4
The antibody binds to the pathologic material and initiates a neutrophil/macrophage response
Other Names:
  • Ch mAb 11-1F4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) of Ch mAb 11-1F4
Time Frame: 2 years approximately
The MTD of a single application of Ch mAb 11-1F4 is defined as the highest safely-tolerated dose (mg/m2) where 0 patients experiences Dose Limiting Toxicity.
2 years approximately

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of subjects with positive amyloid-related organ response
Time Frame: 12 weeks
Amyloid-related organ response will be evaluated on the basis of the accepted criteria per consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis, in patients who completed phase 1b.
12 weeks
Estimated mean area under the curve (AUC) for Ch mAb 11-1F4
Time Frame: Phase 1a: 1, 2, 24 hours post start of infusion; then post-infusion week 1, 2, 3, 4, 8. Phase 1b: pretreatment, 1, 2, 24 hours post start of infusion; then post-infusion week 5, 8, 12.
This is designed to determine the pharmacokinetics of Ch mAb 11-1F4 when given as a single intravenous (i.v.) infusion (phase 1a) or as a series of four weekly intravenous infusions (phase 1b).
Phase 1a: 1, 2, 24 hours post start of infusion; then post-infusion week 1, 2, 3, 4, 8. Phase 1b: pretreatment, 1, 2, 24 hours post start of infusion; then post-infusion week 5, 8, 12.
Number of participants with adverse events
Time Frame: 2 years approximately
This to obtain additional safety data of Ch mAb 11-1F4 when given as a single intravenous infusion (phase 1a) or as a series of four weekly intravenous infusions (phase 1b) by obtaining adverse event information for all subjects during active follow-up visits.
2 years approximately

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Andrew Eisenberger, MD, CUMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2014

Primary Completion (Actual)

July 13, 2017

Study Completion (Actual)

July 13, 2017

Study Registration Dates

First Submitted

September 15, 2014

First Submitted That Met QC Criteria

September 19, 2014

First Posted (Estimated)

September 22, 2014

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 5, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAEL101-101
  • AAAM5108 (Other Identifier: Columbia University)
  • FDA Grant R01FD005110 (Other Grant/Funding Number: FDA OOPD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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