Thalidomide/Dexamethasone Treatment And PET Evaluation In Organ Involvemenet of Cardiac Amyloidosis (TaPiOCA)

October 24, 2017 updated by: Youngil Koh, Seoul National University Hospital

Frontline Thalidomide for Amyloidosis Involving Myocardium: Investigation of Organ Reversing Capacity of Lenalidomide

To prove the organ-reversing potential of thalidomide for amyloidosis with cardiac involvement

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Considering that dismal prognosis of amyloidosis is attributable to organ dysfunction, primary aim of amyloidosis treatment should be an organ reversal. However, due to various reasons, not much is known about organ reversal in amyloidosis. Almost all of the clinical trials evaluated hematologic response in amyloidosis. Meanwhile, besides autologous stem cell transplantation with high-dose melphalan conditioning, hematologic response rate of various agents such as bortezomib, melphalan, thalidomide and lenalidomide are similar for amyloidosis. However, organ reversing potential of these agents is not known. If there is a difference in organ reversing potential despite of similar hematologic response rate, drug with effective organ reversing potential should be a standard treatment for amyloidosis.

The investigators assume that thalidomide could make organ reversal in cardiac amyloidosis due to its specific mechanism of action. To prove this concept, the investigators propose a clinical trial that evaluates organ reversing potential of thalidomide in cardiac amyloidosis.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

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

Study Contact

Study Locations

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age : more than 18 years old

  2. Cardiac amyloidosis (both AL or AH type) patient who meet both (A and B) of the following criteria A. Cardiac involvement: meet one of the following criteria

    • Echocardiography: mean wall thickness >12 mm, and no other cardiac cause
    • NTproBNP >332 ng/l in the absence of renal failure
    • Evidence of cardiac amyloidosis in cardiac MRI B. Treatment history: No history of exposure to thalidomide
  3. ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3
  4. Tolerable major organ function determined by laboratory examination i. Serum creatinine ≤ 3.0 mg/dl ii. Absolute neutrophil count ≥ 1000/μl iii. Platelet ≥ 75000/ μl iv. Hemoglobin ≥ 8.0 mg/dl v. Bilirubin < 2 times or Alkaline phosphate < 4 times upper limit of normal
  5. Expected survival > 3 months
  6. Female participants of child-bearing potential must have a negative pregnancy test prior to treatment and agree to use dual methods of contraception for the duration of the study and for 30 days following completion of study. Male participants must also agree to use a barrier method of contraception for the duration of the study and for 30 days following completion of study if sexually active with a female of child-bearing potential.

Exclusion Criteria:

  1. Amyloidosis without cardiac involvement
  2. Patients who are planning to receive autologous stem cell transplantation
  3. Patients who received autologous stem cell transplantation, remained in hematologic complete response
  4. Pregnant, lactating or unwilling to use adequate contraception
  5. Systemic infection unless specific anti-infective therapy is employed
  6. Known allergies to thalidomide
  7. Previous experimental agents or approved anti-tumor treatment within 1 months before the date of registration

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Thalidomide
Patient with cardiac amyloidosis receive thalilomide with dexamethasone
Drug: Dexamethasone
Drug: Thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematologic response
Time Frame: through study completion, an average of 1 year
Complete response: Normalization of FLC levels and κ to λ ratio, with nega-tive serum and urine immunofixation Very good partial response: de-creased of dFLC to < 40mg/l Partial response: > 50% reduction of dFLC
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiac response
Time Frame: through study completion, an average of 1 year
> 30% and > 300 ng/l decrease in NTproBNP levels in patients with NTproBNP levels ≥ 650 ng/l at base-line or ≥ 2-class decrease in NYHA class in patients with NYHA class 3 or 4 at baseline
through study completion, an average of 1 year
Maximal LV myocardium-blood cavity ratio
Time Frame: through study completion, an average of 1 year
estimated by 11C-Pittsburge B PET imaging
through study completion, an average of 1 year
Overall survival
Time Frame: From date of enrollment until the date of death from any cause, assessed up to 60 months
From date of enrollment until the date of death from any cause, assessed up to 60 months
Progression-free survival
Time Frame: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Toxicity profile related to thalidomide, according to CTCAE version 4.03
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year
Renal response
Time Frame: through study completion, an average of 1 year
> 50% (≥ 5.0 g/d) decrease in 24h urine protein levels in patients with urine protein levels > 0.5 g/l at baseline without ≥ 25% increase in serum creatinine levels or decrease in creatinine clearance from baseline
through study completion, an average of 1 year
Hepatic response
Time Frame: through study completion, an average of 1 year
≥ 50% decrease in alkaline phosphatase levels and/or ≥ 2cm decrease in liver size (assessed by radiograph)
through study completion, an average of 1 year
Mean LV myocardium-blood cavity ratio
Time Frame: through study completion, an average of 1 year
estimated by 11C-Pittsburge B PET imaging
through study completion, an average of 1 year

Collaborators and Investigators

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

Sponsor

Seoul National University Hospital

Collaborators

CW pharmaceutical company

Investigators

  • Principal Investigator: Youngil Koh, MD, PhD, Seoul National University Hospital

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

October 1, 2016

Primary Completion (Anticipated)

September 1, 2019

Study Completion (Anticipated)

September 1, 2019

Study Registration Dates

First Submitted

November 8, 2016

First Submitted That Met QC Criteria

November 16, 2016

First Posted (Estimate)

November 17, 2016

Study Record Updates

Last Update Posted (Actual)

October 26, 2017

Last Update Submitted That Met QC Criteria

October 24, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-1512-129-730

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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