Pomalidomide and Dexamethasone (PDex) in AL Amyloidosis

NCT01510613 | Completed Phase 2 DMC

• 2 other identifiers: AC-007-IT2011-001787-22
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to evaluate the safety and efficacy of Pomalidomide and Dexamethasone in patients who did not achieve a complete response after initial treatment with both an alkylating agent (Melphalan or Cyclophosphamide) and Bortezomib. Patients who received 1 previous treatment without achieving a complete response (CR), but who could not be treated with alkylators and/or Bortezomib due to contraindications, will be included.

Conditions

Primary Amyloidosis of Light Chain Type

Keywords

Pomalidomide; Dexamethasone; treatment; AL amyloidosis

Outcome Measures

Primary Outcomes (1)

• Efficacy of PDex

  To evaluate the efficacy of PDex in patients who did not achieve a complete response after initial treatment with both an alkylating agent (Melphalan or Cyclophosphamide) and Bortezomib.

  evaluation made at the end of each 28 days cycle

Secondary Outcomes (1)

• Safety of PDex

  evaluation made at the end of each 28 days cycle

Study Arms (1)

Pomalidomide and Dexamethasone

EXPERIMENTAL

Drug: Pomalidomide and Dexamethasone

Interventions

Pomalidomide and Dexamethasone DRUG

Pomalidomide: 2-4mg/day, every day in cycles of 28 days until progression or unacceptable toxicity Dexamethasone: 20-40mg/week, on days 1, 8, 15, 22 in cycles of 28 days until progression or unacceptable toxicity

Pomalidomide and Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years.
• Diagnosis of systemic AL amyloidosis.
• Symptomatic organ (heart, kidney, liver, peripheral nervous system, or soft tissue) involvement.
• Patients achieving less than complete response after initial treatment with an alkylating agent (melphalan or cyclophosphamide) and bortezomib. Patients with AL amyloidosis who received 1 previous treatment, but who could not be treated with alkylators and/or bortezomib due to contraindications, will be eligible.
• Measurable disease: difference between amyloidogenic (involved) and uninvolved free light chains (dFLC) \> 50 mg/L.
• Hb ≥ 10 g/dL
• ANC ≥ 1500/uL.
• Platelet count ≥ 100000/uL.
• eGFR ≥ 30 mL/min per 1.73 m2.
• Performance status (ECOG) \< 3.
• Total bilirubin \< 2.5 mg/dL.
• Alkaline phosphatase \< 5 × url.
• ALT \< 3 × url.
• Female: FCBP must have two negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive study drug until the Investigator has verified that the results of these pregnancy tests are negative. Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure. Must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from the study.
• Male: Must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy. Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure. Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from the study.

You may not qualify if:

• Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura as the only evidence of disease.
• New York Heart association (NYHA) class IV.
• Known positivity for HIV or active hepatitis infection.
• Pregnant or nursing women (men must agree to use an acceptable method for contraception for the duration of the study).
• Uncontrolled infections.
• Other active malignancies.
• Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
• Known hypersensitivity to thalidomide or lenalidomide including development of erythema.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

Pavia, 27100, Italy

Location

Related Publications (5)

• Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011 May 10;29(14):1924-33. doi: 10.1200/JCO.2010.32.2271. Epub 2011 Apr 11.

  PMID: 21483018 BACKGROUND

• Palladini G, Russo P, Lavatelli F, Nuvolone M, Albertini R, Bosoni T, Perfetti V, Obici L, Perlini S, Moratti R, Merlini G. Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide. Ann Hematol. 2009 Apr;88(4):347-50. doi: 10.1007/s00277-008-0600-y. Epub 2008 Sep 9.

  PMID: 18779964 BACKGROUND

• Lacy MQ, Hayman SR, Gertz MA, Dispenzieri A, Buadi F, Kumar S, Greipp PR, Lust JA, Russell SJ, Dingli D, Kyle RA, Fonseca R, Bergsagel PL, Roy V, Mikhael JR, Stewart AK, Laumann K, Allred JB, Mandrekar SJ, Rajkumar SV. Pomalidomide (CC4047) plus low-dose dexamethasone as therapy for relapsed multiple myeloma. J Clin Oncol. 2009 Oct 20;27(30):5008-14. doi: 10.1200/JCO.2009.23.6802. Epub 2009 Aug 31.

  PMID: 19720894 BACKGROUND

• Avet-Loiseau H, Soulier J, Fermand JP, Yakoub-Agha I, Attal M, Hulin C, Garderet L, Belhadj K, Dorvaux V, Minvielle S, Moreau P; IFM and MAG groups. Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexamethasone. Leukemia. 2010 Mar;24(3):623-8. doi: 10.1038/leu.2009.273. Epub 2010 Jan 14.

  PMID: 20072152 BACKGROUND

• Palladini G, Milani P, Foli A, Basset M, Russo F, Perlini S, Merlini G. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017 Apr 13;129(15):2120-2123. doi: 10.1182/blood-2016-12-756528. Epub 2017 Jan 27.

  PMID: 28130212 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Giampaolo Merlini, Prof.

  Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Amyloidosis Research and Treatment Center

Study Record Dates

• First Submitted: January 11, 2012
• First Posted: January 16, 2012
• Study Start: February 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 12, 2018

Record last verified: 2018-03

Locations

IT (1)