NL-OMON50586已完成3 期
A Phase 3 Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus MLN9708 or Physician's Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis - MLN9708 (C16011; 0114/0065)
适应症
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 7
研究概览
简要总结
Trial ended prematurely
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •1. Male or female patients 18 years or older., 2. Biopsy-proven diagnosis of AL
- •amyloidosis according to the following standard criteria:, a. Histochemical
- •diagnosis of amyloidosis, as based on tissue specimens with Congo red staining
- •with exhibition of an apple-green birefringence, b. If clinical and laboratory
- •parameters insufficient to establish AL amyloidosis or in cases of doubt,
- •amyloid typing may be necessary (see Section 15.1), 3. Measurable disease as
- •defined by serum differential free light chain concentration
- •(dFLC, difference between amyloid forming [involved] and nonamyloid forming
- •[uninvolved] free light chain [FLC]) >= 50 mg/L)., 4. Objective, measurable
- •major (cardiac or renal ) organ amyloid involvement as defined as follows
- •(amyloid involvement of at least 1 required):
- •a. Cardiac involvement is defined as the presence of a mean left ventricular
- •wall thickness on echocardiogram greater than 12 mm in the absence of other
- •potential causes of left ventricular hypertrophy (controlled hypertension is
- •allowed) with a noncardiac biopsy showing amyloid, or a positive cardiac biopsy
- •in the presence of clinical or laboratory evidence of involvement. If there is
- •isolated cardiac involvement, then typing of amyloid deposists is recommended.
- •b. Renal involvement is defined as proteinuria (predominantly albumin) > 0.5
- •g/day in a 24- hour urine collection
- •Note: Amyloid involvement of other organ systems is allowed, but not required.,
- •5. Must be relapsed or refractory after 1 or 2 prior therapies.
- •For this protocol, relapsed is defined as PD documented more than 60
- •days after last dose; refractory is defined as documented absence of
- •hematologic response or hematologic progression on or within 60 days
- •after last dose of prior therapy.
- •a. Patient must not have been previously treated with proteasome
- •inhibitors. (The sponsor reserves the right to open the study to
- •proteasome inhibitor-exposed patients in the future, at some time point
- •after the first IA. In that case, the patient may not be refractory to
- •proteasome inhibitor therapy.), b. Given that the physician may select from an
- •offered list of regimens to treat a, specific patient, the patient may be
- •refractory to an agent/s listed within the list of offered treatment choices,
- •c. Must have recovered (ie, <= Grade 1 toxicity or patient*s baseline status)
- •from the reversible effects of prior therapy, d. If a patient has received a
- •transplant as his/her first-line therapy, he/she must be, at least 3 months
- •posttransplantation and recovered from the side effects of the, stem cell
- •transplant6. Patient must meet criteria for 1 of the following AL Amyloidosis
- •Risk Stages (as defined, by NT-proBNP cut off of < 332 pg/mL and troponin T
- •cut-off of 0.035 ng/mL as, thresholds):, a. Stage 1: both NT-proBNP and
- •troponin T under threshold, b. Stage 2: either NT-proBNP or troponin T [but not
- •both] over threshold;, c. Stage 3: both NT-proBNP and troponin T over threshold
- •(but NT-proBNP, < 8000 pg/mL), 7. ECOG Performance Status <= 2, 8. Clinical
- •laboratory values:, a. Absolute neutrophil count >= 1000/µL, b. Platelet count
- •>=75,000/µL
- •c. Total bilirubin <= 1.5 x ULN except for patients with Gilbert's syndrome
- •as defined by > 80% unconjugated bilirubin and total bilirubin <= 6
- •mg/dL, d. Alkaline phosphatase <= 5 x ULN,, e. ALT
排除标准
- •Prospective patients will be excluded from this study if they meet ANY of the
- •following criteria:, 1. Amyloidosis due to mutations of the transthyretin gene
- •or presence of other, non-AL amyloidosis., 2. Female patients who are
- •lactating, breastfeeding, or pregnant., 3. Medically documented cardiac
- •syncope, uncompensated NYHA Class 3 or 4 congestive heart failure (Section
- •15.6), myocardial infarction within the previous 6 months, unstable angina
- •pectoris, clinically significant repetitive ventricular arrhythmias despite
- •antiarrhythmic treatment, or severe orthostatic hypotension or clinically
- •important autonomic disease., 4. Clinically overt multiple myeloma, according
- •to the IMGW criteria with at least 1 of the following:
- •a. Bone lesions
- •b. Hypercalcemia, defined as a calcium of > 11 mg/dL, 5. Inability to swallow
- •oral medication, inability or unwillingness to comply with the drug
- •administration requirements, or GI procedure that could interfere with the
- •oral, absorption or tolerance of treatment., 6. Requirement for other
- •concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
- •considered to be investigational or which would be considered as a treatment of
- •AL amyloidosis. However, patients may be on chronic steroids (maximum dose 20
- •mg/day prednisone or equivalent [Section 15.7]) if they are being given for,
- •disorders other than amyloidosis (eg, adrenal insufficiency, rheumatoid
- •arthritis, etc.)., 7. Comorbid 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., 8.
- •Ongoing or active infection, known HIV positive, active hepatitis B or C
- •infection., 9. Psychiatric illness/social situations that would limit
- •compliance with study requirements., 10. Known allergy to boron, MLN9708, any
- •of the study treatments, their
- •analogues, or excipients.
- •11. Systemic treatment with strong CYP3A inducers (rifampin, rifapentine,
- •rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or
- •St. John's wort within 14 days before the first dose of study treatment., 12.
- •Diagnosed or treated for another malignancy with 3 years (or 5 years in France)
- •before study enrollment or previously diagnosed with another malignancy and
- •have any evidence of residual disease. Patients with non-melanoma skin cancer
- •or carcinoma in situ of any type are not excluded if they have undergone
- •complete resection.
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