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Trial record 1 of 4 for:    11-1f4
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Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02245867
First Posted: September 22, 2014
Last Update Posted: July 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Suzanne Lentzsch, MD, Columbia University
  Purpose

The purpose of this study is to examine the tolerance, safety, pharmokinetics, 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 e 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.


Condition Intervention Phase
Amyloidosis Drug: Chimeric Fibril-Reactive Monoclonal Anti-body 11-1F4 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ia/Ib Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Suzanne Lentzsch, MD, Columbia University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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).

  • 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.


Estimated Enrollment: 42
Study Start Date: September 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Ch mAb 11-1F4

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02245867


Locations
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Suzanne Lentzsch, MD
Investigators
Principal Investigator: Suzanne Lentzsch, MD, PhD CUMC
  More Information

Publications:
Solomon, A. and Weiss, D.T. Protein and host factors implicated in the pathogenesis of light chain amyloidosis (AL amyloidosis). Amyloid: Inter. J. Exper. Clin. Invest. 2: 269-279, 1995.

Responsible Party: Suzanne Lentzsch, MD, Professor of Medicine, Dept of Med Hematology & Onc, Columbia University
ClinicalTrials.gov Identifier: NCT02245867     History of Changes
Other Study ID Numbers: AAAM5108
FDA Grant R01FD005110 ( Other Grant/Funding Number: FDA OOPD )
First Submitted: September 15, 2014
First Posted: September 22, 2014
Last Update Posted: July 13, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Suzanne Lentzsch, MD, Columbia University:
Amyloidosis
Relapse
Refractory

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs