AL AmyloidosisPhase 1/2NCT01570387
A Phase I/II Trial of Pomalidomide and Dexamethasone in Subjects With Previously-Treated AL Amyloidosis
A Phase 1/2 study testing Pomalidomide and Dexamethasone in people with AL Amyloidosis, run by Boston Medical Center at 1 site in United States.
Trial summary
This study seeks to enroll patients with AL amyloidosis, for whom treatment with one of the standard melphalan chemotherapy-based regimens is either not recommended or is not their preference. Pomalidomide (CC-4047) is a drug given by mouth, which can change or regulate the functioning of the immune system. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- Pomalidomide and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Apr 2019
- Phase
- Phase 1/2
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
- Understand and voluntarily sign informed consent form.
- ≥18yrs old
- Able to adhere to the study visit schedule and other protocol requirements.
- Biopsy proven tissue amyloid deposits or positive fat aspirate
- Proof of AL type (a or b)
- Measurable plasma cell dyscrasia (a or b and c of the following required):
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- Monoclonal protein in the serum or urine by immunofixation electrophoresis
- Plasmacytosis of bone marrow (<30% plasma cells) with monoclonal staining for kappa or lambda light-chain isotype
- dFLC of 50mg/L (dFLC=difference in involved and uninvolved serum free light-chain levels)
- Must have received ≥1 prior treatment for AL amyloidosis, if it is intensive chemotherapy and an autotransplant it must be ≥6 months prior to enrollment on this study
- Must have recovered from the reversible side effects of any prior therapy; permanent and stable side effects/changes are acceptable. Prior treatment for AL amyloidosis with chemotherapy, thalidomide, lenalidomide or steroids is not an exclusion
- Eastern Cooperative Group (ECOG) performance status ≤2 at study entry
- Lab test results within these ranges:
- Neutrophil ≥1.5 x10e9/L e. Platelets ≥100x10e9/L f. Total bilirubin <1.5mg/dL g. Aspartate aminotransferase (AST or SGOT) and Alanine Aminotransferase (ALT or SGPT) < 2 x Upper limit of normal h. Serum creatinine <2.5mg/dL
- Disease free of prior malignancies for at least 5yrs with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast.
- Females of childbearing potential (FCBP) (a FCBP is a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy, or has not been naturally postmenopausal for at least 24 consecutive months) must have a negative serum or urine pregnancy test with a sensitivity ≥ 50 milli-International unit/mL 10-14 days prior to and again ≤ 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin two (2) acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, ≥ 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to aspirin may use warfarin or low molecular weight heparin).
Who cannot join
- Secondary or familial amyloidosis
- Multiple myeloma (≥30% plasma cells in a bone marrow biopsy specimen or lytic bone lesions)
- Cytotoxic chemo or radiation therapy ≤4 weeks of study entry or following baseline evaluation
- Symptomatic cardiac arrhythmias or O2-dependent restrictive cardiomyopathy
- Dialysis-dependent
- Untreated or uncontrolled infections.
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- Serious medical conditions, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females (lactating females must agree not to breast feed while taking pomalidomide).
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 28 days of baseline.
- Known intolerance to steroids.
- Known hypersensitivity to thalidomide or lenalidomide
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Concurrent use of other anti-cancer agents or treatments.
- Known HIV positivity is not an exclusion, unless cluster of differentiation 4 (CD4) counts <200/microliter and/or patient has multi-drug resistant HIV infections and/or other concurrent AIDS-defining conditions. HIV b-DNA < 75 copies/mL.
Trial locations and contacts
1 site in 1 country.
About this study
This study seeks to enroll patients with AL amyloidosis, for whom treatment with one of the standard melphalan chemotherapy-based regimens is either not recommended or is not their preference.
Pomalidomide (CC-4047) is a drug given by mouth, which can change or regulate the functioning of the immune system. So, in theory, it may reduce or prevent the production of the amyloid protein. Pomalidomide is not currently FDA-approved for AL Amyloidosis. Pomalidomide is chemically similar to thalidomide and lenalidomide, both of these drugs have been approved by the FDA for treatment of patients with multiple myeloma (MM), a disease similar to AL Amyloidosis.
Participants in this study will receive pomalidomide and dexamethasone. Phase I is a dose-escalation study and dose escalation will proceed through 3 dose-levels according to standard rules in which dose levels are started sequentially after complete evaluation of the occurrence of dose-limiting toxicities. In the Phase II portion, participants will receive pomalidomide and dexamethasone using the defined maximum tolerated dose.
Read the detailed description
Primary objective:
Determine dose-limiting toxicity (DLT) and the maximal tolerated dose (MTD) of pomalidomide combined with dexamethasone in subjects with previously- treated light-chain (AL)-amyloidosis
Secondary objectives:
Determine the following at the MTD:
- Hematological complete (CR) very good partial (VGPR) and partial (PR) rates
- duration of response
- organ response
- Time-to-event
- Survival
Exploratory study objective:
To investigate the relationship of changes in the levels of the biomarkers B-type natriuretic peptide (BNP) and troponin I to frequency of specific adverse events and the occurrence of DLT
- Conditions
- AL Amyloidosis
- Being tested
- Pomalidomide, Dexamethasone
- 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.
PomalidomideDrug
Also called pomalyst, imnovist
Cohort 1 = 2 mg/day, Cohort 2 = 3 mg/day, Cohort 3 = 4 mg/day: Days 1-21 of a 28 day cycle
DexamethasoneDrug
Also called Dexamethasone Acetate
10-20 mg on days 1, 8, 15, and 22
| Study group | Role | What they receive |
|---|---|---|
| Phase I - cohort 1 (Pomalidomide 2mg) plus Dexamethasone | Experimental | Pomalidomide 2 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle Receives: Drug: Pomalidomide; Drug: Dexamethasone |
| Phase I - cohort 2 (Pomalidomide 3mg) plus Dexamethasone | Experimental | Pomalidomide 3 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle Receives: Drug: Pomalidomide; Drug: Dexamethasone |
| Phase I - cohort 3 (Pomalidomide 4mg) plus Dexamethasone | Experimental | Pomalidomide 4 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle Receives: Drug: Pomalidomide; Drug: Dexamethasone |
| Phase II Expansion- (Pomalidomide 4mg) plus Dexamethasone | Experimental | Expansion Phase:
Pomalidomide 4 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle Receives: Drug: Pomalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 2 Milligram Dose
Number of patients in Phase I cohort 1 experiencing dose-limiting toxicity at the 2 milligram dose of pomalidomide combined with dexamethasone in subjects with previously- treated light-chain amyloidosis
Measured: one month
Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 3 Milligram Dose
Number of patients in Phase I cohort 2 experiencing dose limiting toxicity in the 3 milligram dose level, cohort 2.
Measured: One month
Assessing Dose-limiting Toxicity to Determine Maximal Tolerated Dosage at 4 Milligram Dose
Number of patients in Phase I cohort 3 experiencing dose-limiting toxicity at the 4 milligram dose for participants within the third dose cohort
Measured: One month
Secondary outcomes (1)
Response to the Maximal Tolerated Dose
Number of participants with a response to treatment at that maximal tolerated dose (including partial, very good, or complete responses)
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2012 (estimated)
- Study startJun 2012
- Primary completionNov 2018
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Vaishali Sanchorawala, MD, Principal investigator, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01570387
- Sponsor's protocol ID
- H-31082
- Other IDs
- PO-AMYL-PI-0024
- Status last verified
- Sep 2020
- First submitted
- 27 Feb 2012
- Last updated
- 22 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sanchorawala V, Shelton AC, Lo S, Varga C, Sloan JM, Seldin DC. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood. 2016 Aug 25;128(8):1059-62. doi: 10.1182/blood-2016-04-710822. Epub 2016 Jul 5.
PubMed 27381904