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

Sponsor
Seoul National University Hospital (Other)
Overall Status
Unknown status
CT.gov ID
NCT02966522
Collaborator
CW pharmaceutical company (Other)
30
Enrollment
1
Location
1
Arm
35
Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Frontline Thalidomide for Amyloidosis Involving Myocardium: Investigation of Organ Reversing Capacity of Lenalidomide
Study Start Date :
Oct 1, 2016
Anticipated Primary Completion Date :
Sep 1, 2019
Anticipated Study Completion Date :
Sep 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Thalidomide

Patient with cardiac amyloidosis receive thalilomide with dexamethasone

Drug: Thalidomide

Drug: Dexamethasone

Outcome Measures

Primary Outcome Measures

  1. Hematologic response [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

Secondary Outcome Measures

  1. Cardiac response [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

  2. Maximal LV myocardium-blood cavity ratio [through study completion, an average of 1 year]

    estimated by 11C-Pittsburge B PET imaging

  3. Overall survival [From date of enrollment until the date of death from any cause, assessed up to 60 months]

  4. Progression-free survival [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]

  5. Toxicity profile related to thalidomide, according to CTCAE version 4.03 [through study completion, an average of 1 year]

  6. Renal response [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

  7. Hepatic response [through study completion, an average of 1 year]

    ≥ 50% decrease in alkaline phosphatase levels and/or ≥ 2cm decrease in liver size (assessed by radiograph)

  8. Mean LV myocardium-blood cavity ratio [through study completion, an average of 1 year]

    estimated by 11C-Pittsburge B PET imaging

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3

  2. 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

  3. Expected survival > 3 months

  4. 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Seoul National University Hospital Seoul Korea, Republic of 03080

Sponsors and Collaborators

  • Seoul National University Hospital
  • CW pharmaceutical company

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Youngil Koh, Clinical professor, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT02966522
Other Study ID Numbers:
  • H-1512-129-730
First Posted:
Nov 17, 2016
Last Update Posted:
Oct 26, 2017
Last Verified:
Oct 1, 2017
Keywords provided by Youngil Koh, Clinical professor, Seoul National University Hospital
Thalidoide
Additional relevant MeSH terms:
Amyloidosis
Thalidomide
Dexamethasone

Study Results

No Results Posted as of Oct 26, 2017