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

Cardiac Amyloidosis Clinical Trial

— TaPiOCA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02966522
• Other study ID #: H-1512-129-730
• Status: Recruiting
• Phase: Phase 2
• First received: November 8, 2016
• Last updated: October 24, 2017
• Start date: October 2016
• Est. completion date: September 2019

Study information

• Verified date: October 2017
• Source: Seoul National University Hospital
• Contact: Ryul Kim, MD
• Email: chrono0707[@]icloud.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Cardiac Amyloidosis

Intervention

Drug:
• Thalidomide

• Dexamethasone

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	CW pharmaceutical company

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (6)

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. — View 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. Epub 2006 Sep 28. — View 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. Review. — View 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. Review. — View 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. — View 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):50-9. doi: 10.1016/j.jcmg.2014.09.018. Epub 2014 Nov 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematologic response	Complete response: Normalization of FLC levels and ? to ? 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	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	through study completion, an average of 1 year
Secondary	Maximal LV myocardium-blood cavity ratio	estimated by 11C-Pittsburge B PET imaging	through study completion, an average of 1 year
Secondary	Overall survival		From date of enrollment until the date of death from any cause, assessed up to 60 months
Secondary	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
Secondary	Toxicity profile related to thalidomide, according to CTCAE version 4.03		through study completion, an average of 1 year
Secondary	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	through study completion, an average of 1 year
Secondary	Hepatic response	= 50% decrease in alkaline phosphatase levels and/or = 2cm decrease in liver size (assessed by radiograph)	through study completion, an average of 1 year
Secondary	Mean LV myocardium-blood cavity ratio	estimated by 11C-Pittsburge B PET imaging	through study completion, an average of 1 year