Pomalidomide and Dexamethasone (PDex) in AL Amyloidosis

March 8, 2018 updated by: Giampaolo Merlini, IRCCS Policlinico S. Matteo

An Open-label, Phase II Study of Pomalidomide and Dexamethasone (PDex) for Previously Treated Patients With AL Amyloidosis.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This will be a phase II open-label single-arm dose-escalation study. Patients with systemic AL amyloidosis who did not achieve a complete response after initial treatment with both an alkylating agent (Melphalan or Cyclophosphamide) and Bortezomib will be enrolled. Patients who received 1 previous treatment, but who could not be treated with alkylators and/or Bortezomib due to contraindications, will be eligible. Twenty-eight patients will be enrolled in the study. The patients will be treated with the combination of Pomalidomide and Dexamethasone given orally in 28 day cycles continuously, i.e. until hematologic or organ progression or unacceptable toxicity. There will be 2 dose levels of Pomalidomide (2 and 4 mg/day). A standard 3+3 dose escalation design will be used. If less than 2 of 6 patient experience dose limiting toxicity at dose level 1, then all other patients will be treated at dose level 2. There will be 2 dose levels also for Dexamethasone (20 and 40 mg/week). The dose of dexamethasone will be adjusted on an individual basis, considering fluid retention and repetitive ventricular arrhythmias at baseline, as well as Dexamethasone-related adverse events. The study comprises 3 periods: screening, treatment (with evaluations of response at the end of every single cycle) followed by the end-of-treatment evaluation and follow-up. After giving written informed consent, subjects will be evaluated for eligibility for enrollment in the study and baseline evaluations will be performed. Treatment will be continued until progression or unacceptable toxicity is observed. After treatment discontinuation, patients will be followed for survival and any possible Second Primary Malignancies signals for 2 years.

Study Type

Interventional

Enrollment (Actual)

28

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 Locations

  • Italy
      • Pavia, Italy, 27100
        • Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

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:

  • 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.

During study participation and for 28 days following discontinuation from the study:

  • All subjects: No more than a 28-day supply of study drug will be dispensed at a time.
  • Female: FCBP with regular cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study discontinuation, and at day 28 following discontinuation from the study. If menstrual cycles are irregular, the pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 28 following discontinuation from the study. In addition to the required pregnancy testing, the Investigator must confirm with FCBP that she is continuing to use two reliable methods of birth control at each visit. Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood. Pregnancy testing and counseling must be performed if a subject misses her period or if her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be discontinued during this evaluation. Females must agree to abstain from breastfeeding during study participation and for at least 28 days after discontinuation from the study.
  • Male: Counseling about the requirement for latex condom use during sexual contact with females of childbearing potential and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood, sperm, or semen.

Exclusion Criteria:

  • 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.
  • Previous or ongoing psychiatric illness (with the exclusion of reactive depression).

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: Pomalidomide and Dexamethasone
Drug: Pomalidomide and Dexamethasone
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of PDex
Time Frame: evaluation made at the end of each 28 days cycle
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of PDex
Time Frame: evaluation made at the end of each 28 days cycle
to assess the safety of PDex combination and to assess the survival of AL Amyloidosis patients treated with PDex.
evaluation made at the end of each 28 days cycle

Collaborators and Investigators

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

Sponsor

IRCCS Policlinico S. Matteo

Investigators

  • Principal Investigator: Giampaolo Merlini, Prof., Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo

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

Helpful Links

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

February 1, 2012

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

January 11, 2012

First Submitted That Met QC Criteria

January 13, 2012

First Posted (Estimate)

January 16, 2012

Study Record Updates

Last Update Posted (Actual)

March 12, 2018

Last Update Submitted That Met QC Criteria

March 8, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-007-IT
  • 2011-001787-22 (EudraCT Number)

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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