Primary Amyloidosis of Light Chain TypePhase 2NCT01510613
Pomalidomide and Dexamethasone (PDex) in AL Amyloidosis
A Phase 2 study testing Pomalidomide and Dexamethasone in people with Primary Amyloidosis of Light Chain Type, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Amyloidosis of Light Chain Type
- What is being tested?
- Pomalidomide and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2012to Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 19Show fewer
- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
1 site in 1 country.
Italy1 site
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
Pavia, 27100
About this study
Official title: 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.
Read the 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.
- Conditions
- Primary Amyloidosis of Light Chain Type
- Being tested
- Pomalidomide and Dexamethasone
- Keywords
- Pomalidomide, Dexamethasone, treatment, AL amyloidosis
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pomalidomide and DexamethasoneDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Pomalidomide and Dexamethasone | Experimental | Not described Receives: Drug: Pomalidomide and Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: evaluation made at the end of each 28 days cycle
Secondary outcomes (1)
Safety of PDex
to assess the safety of PDex combination and to assess the survival of AL Amyloidosis patients treated with PDex.
Measured: evaluation made at the end of each 28 days cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2012 (estimated)
- Study startFeb 2012
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary Amyloidosis of Light Chain TypeStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giampaolo Merlini, Fondazione IRCCS Policlinico San Matteo di Pavia
- Investigators
- Giampaolo Merlini, Prof., Principal investigator, Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01510613
- Sponsor's protocol ID
- AC-007-IT
- Other IDs
- 2011-001787-22
- Status last verified
- Mar 2018
- First submitted
- 11 Jan 2012
- Last updated
- 12 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 21483018Palladini 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.
PubMed 18779964Lacy 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.
PubMed 19720894Avet-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.
PubMed 20072152Palladini 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.
PubMed 28130212
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase II Study of Pomalidomide and Dexamethasone (PDex) for Previously Treated Patients With AL Amyloidosis.
- ClinicalTrials.gov ID
- NCT01510613
- Acronym / sponsor ID
- AC-007-IT
- Conditions
- Primary Amyloidosis of Light Chain Type
- Keywords
- Pomalidomide, Dexamethasone, treatment, AL amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 16 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pomalidomide and Dexamethasone | Experimental | Drug: Pomalidomide and Dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pomalidomide and DexamethasonePomalidomide: 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 | Drug | Pomalidomide and Dexamethasone |
Primary outcome
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.
1 secondary outcome
Safety of PDex
Time frame: evaluation made at the end of each 28 days cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2018.
- Background: PubMed 21483018Merlini 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.
- Background: PubMed 18779964Palladini 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.
- Background: PubMed 19720894Lacy 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.
- Background: PubMed 20072152Avet-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.
- Derived from this study: PubMed 28130212Palladini 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giampaolo Merlini, Prof. principal investigator
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico S.Matteo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pomalidomide and Dexamethasone in people with Primary Amyloidosis of Light Chain Type, run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of PDex (time frame: evaluation made at the end of each 28 days cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01510613, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2018.