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

Primary Purpose

Cardiac Amyloidosis

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Thalidomide

Dexamethasone

About this trial

This is an interventional treatment trial for Cardiac Amyloidosis focused on measuring Thalidoide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age : more than 18 years old
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
ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3
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
Expected survival > 3 months
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:

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

Sites / Locations

Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Thalidomide

Arm Description

Patient with cardiac amyloidosis receive thalilomide with dexamethasone

Outcomes

Primary Outcome Measures

Hematologic response

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

Cardiac response

> 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

Maximal LV myocardium-blood cavity ratio

estimated by 11C-Pittsburge B PET imaging

Overall survival

Progression-free survival

Toxicity profile related to thalidomide, according to CTCAE version 4.03

Renal response

> 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

Hepatic response

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

Mean LV myocardium-blood cavity ratio

estimated by 11C-Pittsburge B PET imaging

Full Information

NCT ID

NCT02966522

First Posted

November 8, 2016

Last Updated

October 24, 2017

Sponsor

Seoul National University Hospital

Collaborators

CW pharmaceutical company

1. Study Identification

Unique Protocol Identification Number

NCT02966522

Brief Title

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

Acronym

TaPiOCA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Unknown status

Study Start Date

October 2016 (undefined)

Primary Completion Date

September 2019 (Anticipated)

Study Completion Date

September 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Seoul National University Hospital

Collaborators

CW pharmaceutical company

4. Oversight

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiac Amyloidosis

Keywords

Thalidoide

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Thalidomide

Arm Type

Experimental

Arm Description

Patient with cardiac amyloidosis receive thalilomide with dexamethasone

Intervention Type

Drug

Intervention Name(s)

Thalidomide

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Primary Outcome Measure Information:

Title

Hematologic response

Description

Time Frame

through study completion, an average of 1 year

Secondary Outcome Measure Information:

Title

Cardiac response

Description

> 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

Time Frame

through study completion, an average of 1 year

Title

Maximal LV myocardium-blood cavity ratio

Description

estimated by 11C-Pittsburge B PET imaging

Time Frame

through study completion, an average of 1 year

Title

Overall survival

Time Frame

From date of enrollment until the date of death from any cause, assessed up to 60 months

Title

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

Title

Toxicity profile related to thalidomide, according to CTCAE version 4.03

Time Frame

through study completion, an average of 1 year

Title

Renal response

Description

Time Frame

through study completion, an average of 1 year

Title

Hepatic response

Description

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

Time Frame

through study completion, an average of 1 year

Title

Mean LV myocardium-blood cavity ratio

Description

estimated by 11C-Pittsburge B PET imaging

Time Frame

through study completion, an average of 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age : more than 18 years old 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 ECOG(Eastern Cooperative Oncology Group) performance status ≤ 3 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 Expected survival > 3 months 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: Amyloidosis without cardiac involvement Patients who are planning to receive autologous stem cell transplantation Patients who received autologous stem cell transplantation, remained in hematologic complete response Pregnant, lactating or unwilling to use adequate contraception Systemic infection unless specific anti-infective therapy is employed Known allergies to thalidomide Previous experimental agents or approved anti-tumor treatment within 1 months before the date of registration

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ryul Kim, MD

chrono0707@icloud.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Youngil Koh, MD, PhD

Organizational Affiliation

Seoul National University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Youngil Koh, MD, PhD

go01@snu.ac.kr

First Name & Middle Initial & Last Name & Degree

Ryul Kim, MD

chrono0707@icloud.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

26491974

Citation

Kastritis E, Dimopoulos MA. Recent advances in the management of AL Amyloidosis. Br J Haematol. 2016 Jan;172(2):170-86. doi: 10.1111/bjh.13805. Epub 2015 Oct 22.

Results Reference

background

PubMed Identifier

23294331

Citation

Gatt ME, Palladini G. Light chain amyloidosis 2012: a new era. Br J Haematol. 2013 Mar;160(5):582-98. doi: 10.1111/bjh.12191. Epub 2013 Jan 7.

Results Reference

background

PubMed Identifier

22493299

Citation

Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, Dingli D, Zeldenrust SR, Mikhael JR, Hall R, Rajkumar SV, Reeder C, Fonseca R, Bergsagel PL, Stewart AK, Roy V, Witzig TE, Lust JA, Russell SJ, Gertz MA, Lacy MQ. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012 Jun 7;119(23):5397-404. doi: 10.1182/blood-2012-02-413161. Epub 2012 Apr 4.

Results Reference

background

PubMed Identifier

17008538

Citation

Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, Lust JA, Allred JB, Witzig TE, Rajkumar SV, Greipp PR, Russell SJ, Kabat B, Gertz MA. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007 Jan 15;109(2):465-70. doi: 10.1182/blood-2006-07-032987. Epub 2006 Sep 28.

Results Reference

background

PubMed Identifier

22517904

Citation

Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, Marinaki S, Apostolou T, Nikitas N, Gkortzolidis G, Michalis E, Delimpasi S, Dimopoulos MA. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012 Jun 7;119(23):5384-90. doi: 10.1182/blood-2011-12-396903. Epub 2012 Apr 18.

Results Reference

background

PubMed Identifier

25499132

Citation

Lee SP, Lee ES, Choi H, Im HJ, Koh Y, Lee MH, Kwon JH, Paeng JC, Kim HK, Cheon GJ, Kim YJ, Kim I, Yoon SS, Seo JW, Sohn DW. 11C-Pittsburgh B PET imaging in cardiac amyloidosis. JACC Cardiovasc Imaging. 2015 Jan;8(1):50-59. doi: 10.1016/j.jcmg.2014.09.018. Epub 2014 Nov 4.

Results Reference

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

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