Ixazomib In Combination With Cyclophosphamide And Dexamethasone for Newly Diagnosed AL Amyloidosis

NCT03236792 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: GCO 16-1853
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

Light chain (AL) amyloidosis is a bone marrow disorder that affects a wide range of organs that can lead to organ dysfunction and death. Amyloid is an abnormal protein that is produced in your bone marrow and cannot be broken down. It builds up in different organs preventing them from working well. The most commonly affected organs are the kidneys, heart, liver, spleen, nervous system, and digestive tract. Treatment with chemotherapy can stop the growth of abnormal cells that produce this abnormal protein. Decrease in amyloid protein in the body improves the function of the affected organs. The primary purpose of this study is to determine the safest dose of the medications and how well you tolerate them or the "maximum tolerated dose" (MTD). The study uses Ixazomib in combination with cyclophosphamide and dexamethasone to treat people with newly diagnosed AL amyloidosis. This combination of medications is an oral regimen that is taken over 6 cycles. The first part of study will determine the safety of this regimen and the second part of the study will determine how effective this combination of drugs is to treat your disease.

Conditions

AL Amyloidosis

Keywords

Newly Diagnosed; AL Amyloidosis; Amyloid; Light chain Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The MTD of ixazomib given in combination with cyclophosphamide and dexamethasone, 3 + 3 design in Phase 1 of this study

  up to 3 years

Secondary Outcomes (2)

• Response Rate

  up to 3 years

• Frequency of organ response

  up to 3 years

Study Arms (1)

Newly Diagnosed AL Amyloidosis

EXPERIMENTAL

Ixazomib/Cyclophosphamide/Dexamethasone. Treatment cycles will be repeated up to 6 cycles or until disease progression or until development of significant treatment-related toxicities.

Drug: Ixazomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

3 mg or 4mg of Ixazomib will be taken orally on days 1, 8, and 15 of a 28-day cycle

Newly Diagnosed AL Amyloidosis

Cyclophosphamide DRUG

300, 400, or 500 mg of oral Cyclophosphamide on days 1, 8, and 15 of a 28-day cycle

Newly Diagnosed AL Amyloidosis

Dexamethasone DRUG

20 mg of oral Dexamethasone on days 1, 8, 15, 22 in a 28-day cycle

Newly Diagnosed AL Amyloidosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years or older.
• Biopsy-proven diagnosis of AL amyloidosis according to the following standard criteria:
• Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
• If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary
• Measurable disease defined by serum differential free light chain concentration (difference between amyloid forming \[involved\] and non amyloid forming \[uninvolved\] free light chain \[FLC\]) ≥ 50 mg/L).
• Amyloid organ involvement including renal, cardiac, GI and/or nervous system involvement as well as soft tissue disease
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥1,000/mm3 and platelet count ≥75,000/mm3.
• Hemoglobin ≥ 8.0 g/dL
• Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
• Total bilirubin ≤ 2 the upper limit of the normal range (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 x ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 ULN.
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault Formula).

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• Major surgery within 14 days before enrollment.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
• Evidence of current uncontrolled cardiovascular conditions:
• uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, \*unstable angina, or myocardial infarction within the past 6 months.
• Recent history of myocardial infarction in the six months prior to registration
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with early stage prostate cancer, non melanoma skin cancer or carcinoma in situ of any type are not excluded; patients with malignancies that have undergone complete resection are not excluded.
• Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
• Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21days of the start of this trial and throughout the duration of this trial.
• New York Heart Association Class III or IV Heart Failure

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (3)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Alzheimer Disease

Interventions

ixazomib; Cyclophosphamide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Keren Osman, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: August 2, 2017
• Study Start: June 12, 2017
• Primary Completion: September 20, 2022
• Study Completion: September 20, 2022
• Last Updated: September 29, 2022

Record last verified: 2022-09

Locations

US (3)