Pomalidomide and Dexamethasone (PDex) in AL Amyloidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by IRCCS Policlinico S. Matteo
Sponsor:
Information provided by (Responsible Party):
Giampaolo Merlini, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier:
NCT01510613
First received: January 11, 2012
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Primary Amyloidosis of Light Chain Type
Drug: Pomalidomide and Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Phase II Study of Pomalidomide and Dexamethasone (PDex) for Previously Treated Patients With AL Amyloidosis.

Resource links provided by NLM:


Further study details as provided by IRCCS Policlinico S. Matteo:

Primary Outcome Measures:
  • Efficacy of PDex [ Time Frame: evaluation made at the end of each 28 days cycle ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Safety of PDex [ Time Frame: evaluation made at the end of each 28 days cycle ] [ Designated as safety issue: Yes ]
    to assess the safety of PDex combination and to assess the survival of AL Amyloidosis patients treated with PDex.


Estimated Enrollment: 28
Study Start Date: February 2012
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01510613

Contacts
Contact: Giampaolo Merlini, Prof. +39(0)382502994 gmerlini@unipv.it
Contact: Giovanni Palladini, Dr. +39(0)382502994 g.palladini@smatteo.pv.it

Locations
Italy
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo Recruiting
Pavia, Italy, 27100
Contact: Giovanni Palladini, Dr.    +39(0)382502994    g.palladini@smatteo.pv.it   
Contact: Leda Roggeri, Dr.    +39(0)382502994    leda78@gmail.com   
Principal Investigator: Giampaolo Merlini, Prof.         
Sub-Investigator: Giovanni Palladini, Dr.         
Sponsors and Collaborators
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
  More Information

Additional Information:
Publications:
Responsible Party: Giampaolo Merlini, Director, Amyloidosis Research and Treatment Center, IRCCS Policlinico S. Matteo
ClinicalTrials.gov Identifier: NCT01510613     History of Changes
Other Study ID Numbers: AC-007-IT, 2011-001787-22
Study First Received: January 11, 2012
Last Updated: November 30, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by IRCCS Policlinico S. Matteo:
Pomalidomide
Dexamethasone
treatment
AL amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Metabolic Diseases
Proteostasis Deficiencies
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Pomalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Growth Inhibitors
Growth Substances
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 22, 2014