A Phase I/II Trial of Pomalidomide and Dexamethasone in Subjects With Previously-Treated AL Amyloidosis
2 other identifiers
interventional
27
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jun 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 27, 2012
CompletedFirst Posted
Study publicly available on registry
April 4, 2012
CompletedStudy Start
First participant enrolled
June 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2019
CompletedResults Posted
Study results publicly available
December 16, 2019
CompletedSeptember 22, 2020
September 1, 2020
6.4 years
February 27, 2012
November 1, 2019
September 3, 2020
Conditions
Outcome Measures
Primary Outcomes (3)
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
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.
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
One month
Secondary Outcomes (1)
Response to the Maximal Tolerated Dose
one year
Study Arms (4)
Phase I - cohort 1 (Pomalidomide 2mg) plus Dexamethasone
EXPERIMENTALPomalidomide 2 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle
Phase I - cohort 2 (Pomalidomide 3mg) plus Dexamethasone
EXPERIMENTALPomalidomide 3 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle
Phase I - cohort 3 (Pomalidomide 4mg) plus Dexamethasone
EXPERIMENTALPomalidomide 4 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle
Phase II Expansion- (Pomalidomide 4mg) plus Dexamethasone
EXPERIMENTALExpansion Phase: Pomalidomide 4 mg/day on days 1-28 plus dexamethasone 10-20 mg on days 1-21 of a 28 day cycle
Interventions
Cohort 1 = 2 mg/day, Cohort 2 = 3 mg/day, Cohort 3 = 4 mg/day: Days 1-21 of a 28 day cycle
10-20 mg on days 1, 8, 15, and 22
Eligibility Criteria
You may qualify if:
- 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):
- 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
- Eastern Cooperative Group (ECOG) performance status ≤2 at study entry
- Lab test results within these ranges:
- d. 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.
- +1 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Boston Medical Centerlead
- Celgene Corporationcollaborator
Study Sites (1)
Boston Medical Center
Boston, Massachusetts, 02118, United States
Related Publications (1)
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.
PMID: 27381904DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Vaishali Sanchorawala
- Organization
- Boston Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Vaishali Sanchorawala, MD
Boston Medical Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 27, 2012
First Posted
April 4, 2012
Study Start
June 1, 2012
Primary Completion
November 1, 2018
Study Completion
April 1, 2019
Last Updated
September 22, 2020
Results First Posted
December 16, 2019
Record last verified: 2020-09
Data Sharing
- IPD Sharing
- Will not share