Bortezomib, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Light Chain Amyloidosis

NCT01072773 | Completed Phase 2 Results DMC

• 4 other identifiers: MC0985NCI-2009-0156409-005736X05306
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bortezomib, cyclophosphamide, and dexamethasone together works in treating patients with primary systemic light chain amyloidosis.

Conditions

Primary Systemic Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Confirmed Hematologic Response

  Response that was confirmed on 2 consecutive evaluations during treatment. Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and \<5% plasma cells in bone marrow. Very Good Partial Response(VGPR): \>=90% reduction in serum M-component; Urine M-Component \<=100 mg per 24 hours. Partial Response(PR): \>=50% reduction in serum M-component and/or Urine M-Component \>=90% reduction or \<200 mg per 24 hours; or \>=50% decrease in difference between involved and uninvolved FLC levels.

  Duration of treatment (up to 12 cycles/months)

Secondary Outcomes (5)

• Number of Participants With Treatment Related Adverse Events.

  Duration on treatment (up to 12 cycles/months)

• Number of Participants With an Organ Response.

  Duration on treatment (up to 12 cycles/months)

• Overall Survival

  Duration of Study (up to 5 years)

• Time to Disease Progression

  Duration of Study (up to 5 years)

• Duration of Response

  Duration of Study (up to 5 years)

Study Arms (1)

Bortez/Cyc/Dex

EXPERIMENTAL

Bortezomib IV on days 1, 8, and 15, oral cyclophosphamide and oral dexamethasone once daily on days 1, 8, 15, and 22.

Drug: bortezomib; Drug: cyclophosphamide; Drug: dexamethasone

Interventions

bortezomib DRUG

1.3 mg/m\^2, by IV on days 1, 8 and 15 every 28 days

Also known as: LDP 341, MLN341, PS-341, VELCADE

Bortez/Cyc/Dex

cyclophosphamide DRUG

300 mg/m\^2, orally, on days 1, 8, 15 \& 22 every 28 days.

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Bortez/Cyc/Dex

dexamethasone DRUG

40 mg, orally, on days 1, 8, 15 \& 22 every 28 days

Also known as: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM

Bortez/Cyc/Dex

Eligibility Criteria

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

You may qualify if:

• Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens
• Measurable disease of amyloid light chain amyloidosis as defined by at least ONE of the following: serum monoclonal protein \>= 1.0 g by protein electrophoresis, \> 200 mg of monoclonal protein in the urine on 24 hour electrophoresis, serum free light-chain \>= 7.5 mg/dL with an abnormal kappa:lambda ratio
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
• Absolute neutrophil count \>= 1000/uL
• Platelet \>= 75000/uL
• Total bilirubin \< 3.0 mg/dL
• Aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN)
• Creatinine clearance \>= 30ml/min
• Women of childbearing potential should have a negative serum or urine pregnancy test done =\< 7 days prior to registration, and should be willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
• Male subject agrees to use an acceptable method for contraception for the duration of the study
• Previously treated amyloidosis; no limit to prior therapy provided there is adequate residual organ function
• Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system or soft tissue); carpal tunnel syndrome skin purpura, or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"
• Renal involvement is defined as proteinuria (predominantly albumin) \> 0.5 g/day in a 24- hour urine collection
• Cardiac involvement is defined as the presence of a mean left ventricular wall thickness on echocardiogram greater than 12 mm in the absence of a history of hypertension or valvular heart disease, or in the presence of unexplained low voltage (\< 0.5 mV) on the electrocardiogram
• Hepatic involvement is defined as hepatomegaly (\>= 2 cm below costal margin) on physical exam or an alkaline phosphatase \> 1.5 x ULN

You may not qualify if:

• Melphalan or other myelosuppressive agents =\< 3 weeks prior to registration; non-myelosuppressive agents like thalidomide, or high dose corticosteroids \<= 1week prior to registration
• Concurrent use of corticosteroids, but patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than amyloid, i.e., adrenal insufficiency, rheumatoid arthritis, etc
• Any of the following because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: pregnant women and nursing women
• Other active malignancy =\< 2 years prior to registration; EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving any specific treatment for their cancer
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including psychiatric illness/social situations that would limit compliance with study requirements
• Known to be HIV positive
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Clinically overt multiple myeloma (monoclonal Bone Marrow Plasma Count \> 30%), and at least one of the following: bone lesions or hypercalcemia
• History of myocardial infarction =\< 6 months, or requiring use of ongoing maintenance drug therapy for life-threatening ventricular arrhythmias
• Grade 3 sensory or grade 1 painful peripheral neuropathy
• Known hypersensitivity to bortezomib, boron or mannitol
• Cardiac syncope, uncompensated New York Heart Association (NYHA) Class 3 or 4 congestive heart failure or troponin T \> 0.1 ng/mL

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

Bortezomib; Cyclophosphamide; Dexamethasone; Calcium Dobesilate

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Shaji Kumar
• Organization: Mayo Clinic

kumar.shaji@mayo.edu

Study Officials

• Shaji Kumar, M.D.

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2010
• First Posted: February 22, 2010
• Study Start: March 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: June 1, 2012
• Last Updated: April 2, 2014
• Results First Posted: December 5, 2012

Record last verified: 2014-03

Locations

US (1)