A Phase I/II Trial of Pomalidomide and Dexamethasone in Subjects With Previously-Treated AL Amyloidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Boston Medical Center
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Boston Medical Center
ClinicalTrials.gov Identifier:
NCT01570387
First received: February 27, 2012
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
AL Amyloidosis
Drug: Pomalidomide
Drug: Dexamthasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Pomalidomide and Dexamethasone in Subjects With Previously-Treated AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Boston Medical Center:

Primary Outcome Measures:
  • Determining dose-limiting toxicity and maximal tolerated dosage [ Time Frame: one month ] [ Designated as safety issue: Yes ]
    Determine dose-limiting toxicity (DLT) and the maximal tolerated dose (MTD) of pomalidomide combined with dexamethasone in subjects with previously- treated light-chain (AL)-amyloido


Secondary Outcome Measures:
  • Response to the maximal tolerated dose [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    Patient response to treatment


Estimated Enrollment: 35
Study Start Date: June 2012
Estimated Study Completion Date: February 2030
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: all patients on study
All patients enrolled at a specific dose level will receive the same treatment. There will be no randomization and no placebos.
Drug: Pomalidomide
Cohort 1 = 2 mg/day, Cohort 2 = 3 mg/day, Cohort 3 = 4 mg/day: Days 1-28
Drug: Dexamthasone
10-20 mg on days 1, 8, 15, and 22

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 BNP and troponin I to frequency of specific adverse events and the occurrence of DLT

  Eligibility

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

Inclusion Criteria:

  1. Understand and voluntarily sign an informed consent form (ICF).
  2. ≥18yrs old at study entry.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. Biopsy proven tissue amyloid deposits or positive fat aspirate
  5. Proof of AL type (a or b)
  6. Measurable plasma cell dyscrasia (a or b and c of the following required):

    1. Monoclonal protein in the serum or urine by immunofixation electrophoresis
    2. Plasmacytosis of bone marrow (<30% plasma cells) with monoclonal staining for kappa or lambda light-chain isotype
    3. dFLC of 50mg/L (dFLC=difference in involved and uninvolved serum free light-chain levels)
  7. 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
  8. 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
  9. SWOG performance status ≤2 at study entry
  10. Laboratory test results within these ranges:

    d. Neutrophil ≥1.5 x10e9/L e. Platelets ≥100x10e9/L f. Total bilirubin <1.5mg/dL g. AST (SGOT) and ALT (SGPT) <2xULN h. Serum creatinine <2.5mg/dL

  11. 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.
  12. 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 mIU/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 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.
  13. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

  1. Secondary or familial amyloidosis
  2. Multiple myeloma (≥30% plasma cells in a bone marrow biopsy specimen or lytic bone lesions)
  3. Cytotoxic chemotherapy or radiation therapy ≤4 weeks of study entry or following baseline evaluation
  4. Symptomatic cardiac arrhythmias or O2-dependent restrictive cardiomyopathy
  5. Dialysis-dependent
  6. Untreated or uncontrolled infections.
  7. Serious medical conditions, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF.
  8. Pregnant or breast feeding females (lactating females must agree not to breast feed while taking pomalidomide).
  9. 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.
  10. Use of any other experimental drug or therapy within 28 days of baseline.
  11. Known intolerance to steroids.
  12. Known hypersensitivity to thalidomide or lenalidomide
  13. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  14. Concurrent use of other anti-cancer agents or treatments.
  15. Known HIV positivity is not an exclusion, unless CD4 counts <200/mcL and/or patient has multi-drug resistant HIV infections and/or other concurrent AIDS-defining conditions. HIV b-DNA < 75 copies/mL.
  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: NCT01570387

Contacts
Contact: Sally Fennessey 617-638-8265 sally.fennessey@bmc.org

Locations
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Sally Fennessey    617-638-8265    sally.fennessey@bmc.org   
Sponsors and Collaborators
Boston Medical Center
Celgene Corporation
Investigators
Principal Investigator: Vaishali Sanchorawala, MD Boston Medical Center
  More Information

No publications provided

Responsible Party: Boston Medical Center
ClinicalTrials.gov Identifier: NCT01570387     History of Changes
Other Study ID Numbers: H-31082, PO-AMYL-PI-0024
Study First Received: February 27, 2012
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amyloidosis
Metabolic Diseases
Proteostasis Deficiencies
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Pomalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating 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
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014