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Phase II Study of Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Light Chain Amyloidosis

Phase 2
18 Years
Not Enrolling
Primary Systemic Amyloidosis

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Trial Information

Phase II Study of Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Light Chain Amyloidosis


I. To assess the confirmed hematologic response rate (ACR + VGPR + PR) of the combination of
bortezomib, cyclophosphamide and dexamethasone in patients with primary systemic


I. Organ response rate of the bortezomib, cyclophosphamide and dexamethasone combination.

II. Severity and frequency of adverse events associated with bortezomib, cyclophosphamide
and dexamethasone treatment in patients with primary systemic amyloidosis.

III. Time to progression.

IV. Survival.

OUTLINE: Patients receive bortezomib IV on days 1, 8, and 15 and oral cyclophosphamide and
oral dexamethasone once daily on days 1, 8, 15, and 22. Treatment repeats every 28 days for
up to 12 courses in the absence of disease progression or unacceptable toxicity. After
completion of study treatment, patients are followed every 6 months for 2 years.

Inclusion Criteria:

- Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy
of green birefringent material in Congo red-stained tissue specimens

- Measurable disease of AL 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

- ECOG Performance Status (PS) 0, 1 or 2

- Absolute neutrophil count >= 1000/uL

- Platelet >= 75000/uL

- Total bilirubin < 3.0 mg/dL

- AST =< 3 x 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

- Peripheral nerve involvement is defined based on clinical history or abnormal sensory
and/or motor findings on neurologic exam

- Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or
dysgeusia, gastric atony by gastric emptying scan, diarrhea or constipation

- Soft tissue and lymphatic involvement may be ascertained based on classic physical
exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome,
synovial enlargement, firm enlarged lymph nodes) or biopsy

- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by subject any time without prejudice to future medical care

- Willingness to return to Mayo Clinic enrolling institution for follow-up

Exclusion Criteria:

- 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 NYHA Class 3 or 4 congestive heart failure or troponin
T > 0.1 ng/mL

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With a Confirmed Hematologic Response

Outcome Description:

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.

Outcome Time Frame:

Duration of treatment (up to 12 cycles/months)

Safety Issue:


Principal Investigator

Shaji Kumar, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

June 2012

Related Keywords:

  • Primary Systemic Amyloidosis
  • Amyloidosis



Mayo Clinic Rochester, Minnesota  55905