Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis
A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis
RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop plasma cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may be an effective treatment for primary systemic amyloidosis.
PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with primary systemic amyloidosis.
調査の概要
詳細な説明
OBJECTIVES:
Primary
* Assess the hematologic response rate in patients with primary systemic amyloidosis treated with lenalidomide, cyclophosphamide, and dexamethasone.
Secondary
- Determine the organ response rate in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the time to progression in patients treated with this regimen.
- Determine the survival of patients treated with this regimen.
OUTLINE: Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide* on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive cyclophosphamide for up to 1 year. After completion of study treatment, patients are followed every 6 months for up to 3 years.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
-
-
Arizona
-
Scottsdale、Arizona、アメリカ、85259-5499
- Mayo Clinic in Arizona
-
-
Florida
-
Jacksonville、Florida、アメリカ、32224
- Mayo Clinic in Florida
-
-
Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
DISEASE CHARACTERISTICS:
- Histochemical diagnosis of AL amyloidosis based on detection of green birefringent material in Congo red-stained tissue specimens by polarizing microscopy
Measurable disease, as defined by one of the following:
- Serum monoclonal protein ≥ 1.0 g by serum electrophoresis
- Urine monoclonal protein > 200 mg by 24-hour urine electrophoresis
- Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Symptomatic organ involvement with amyloid to justify therapy
- May include liver involvement, cardiac involvement, renal involvement, grade 1 peripheral neuropathy, or soft tissue involvement
- Must have more than skin purpura or carpal tunnel syndrome
No amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as only evidence of disease
- Vascular amyloid only in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis
- No clinically overt multiple myeloma (i.e., monoclonal BMPC > 30%, bone lesions, or hypercalcemia)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,000/μL
- Platelet count ≥ 75,000/μL
- Creatinine < 3.0 mg/dL
- Not pregnant
- Negative pregnancy test
- Fertile patients must use two acceptable methods of contraception for ≥ 28 days prior to, during, and for ≥ 28 days after completion of study treatment
- No nursing during and for ≥ 28 days after completion of study treatment
- No blood, semen, or sperm donation during and for ≥ 28 days after completion of study treatment
- No malignancies within the past 5 years except treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
- No neuropathy ≥ grade 2, defined as motor neuropathy (symptomatic weakness interfering with function, but not interfering with activities of daily living [ADL]) or sensory neuropathy (sensory alteration or paresthesia [including tingling], interfering with function, but not interfering with ADL)
- No uncontrolled infection
- No syncope within the past 30 days
- No known hypersensitivity to thalidomide, including desquamating rash with thalidomide in the past
- No known seropositivity for HIV
- No active hepatitis A, B, or C
- No New York Heart Association class III or IV heart disease
- No venous thromboembolic event within the past 42 days
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation - Patients intolerant to aspirin may use low molecular weight heparin
PRIOR CONCURRENT THERAPY:
- No prior lenalidomide
- More than 2 weeks since prior and no other concurrent anticancer agents or treatments
- More than 4 weeks since prior experimental agents
- No other concurrent corticosteroids except chronic steroids (maximum dose 20 mg/day of prednisone equivalent) for disorders other than amyloidosis (e.g., adrenal insufficiency or rheumatoid arthritis)
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:CRD
Lenalidomide 15mg daily (days 1-21) Cyclophosphamide 300 mg/m^2 (days 1, 8, 15) Dexamethasone 40 mg weekly |
300 mg/m^2 days 1, 8 & 15 of a 28 day cycle taken orally with food
40 mg weekly taken orally
15 mg daily days 1-21 of a 28 day cycle taken orally with food
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
時間枠:Duration on study (up to 3 years)
|
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 on study (up to 3 years)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Number of Patients With Organ Response
時間枠:Duration of study (up to 3 years)
|
Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid. Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%. |
Duration of study (up to 3 years)
|
Number of Participants With Severe Adverse Events
時間枠:Duration of study (up to 3 years)
|
Severe adverse events were defined as grade 3 or higher, at least possibly related to study drugs.
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
|
Duration of study (up to 3 years)
|
Progression Free Survival (PFS)
時間枠:Duration of study (up to 3 years)
|
Progression free survival (PFS) was defined as the time from registration to hematologic progression or death of any cause.
Progression free and alive patients were censored at the date of last follow-up.
The median PFS with 95% CI was estimated using the Kaplan Meier method.
|
Duration of study (up to 3 years)
|
Overall Survival (OS)
時間枠:Duration of study (up to 3 years)
|
Overall survival (OS) was defined as the time from registration to death of any cause.
Surviving patients were censored at the date of last follow-up.
The median OS with 95% CI was estimated using the Kaplan Meier method.
|
Duration of study (up to 3 years)
|
協力者と研究者
スポンサー
捜査官
- スタディチェア:Shaji K. Kumar, MD、Mayo Clinic
- 主任研究者:Craig B. Reeder, MD、Mayo Clinic
- 主任研究者:Vivek Roy, MD, FACP、Mayo Clinic
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
- 心血管疾患
- 血管疾患
- 代謝疾患
- 免疫系疾患
- 組織型別の新生物
- 新生物
- リンパ増殖性疾患
- 免疫増殖性疾患
- 血液疾患
- 出血性疾患
- 止血障害
- パラタンパク血症
- 血液タンパク質障害
- プロテオスタシス欠損症
- 多発性骨髄腫
- 新生物、形質細胞
- 免疫グロブリン軽鎖アミロイドーシス
- アミロイドーシス
- 形質細胞腫
- 薬の生理作用
- 薬理作用の分子機構
- 自律神経剤
- 末梢神経系エージェント
- 抗炎症剤
- 抗リウマチ剤
- 抗悪性腫瘍薬
- 免疫抑制剤
- 免疫学的要因
- 制吐薬
- 胃腸薬
- グルココルチコイド
- ホルモン
- ホルモン、ホルモン代替物、およびホルモン拮抗薬
- 抗腫瘍剤、ホルモン剤
- 抗悪性腫瘍薬、アルキル化
- アルキル化剤
- 骨髄破壊的アゴニスト
- 血管新生阻害剤
- 血管新生調節剤
- 成長物質
- 成長阻害剤
- デキサメタゾン
- シクロホスファミド
- レナリドミド
その他の研究ID番号
- MC0685 (その他の識別子:Mayo Clinic Cancer Center)
- P30CA015083 (米国 NIH グラント/契約)
- NCI-2010-01954 (その他の識別子:NCI CTRP)
- 06-005711 (その他の識別子:Mayo Clinic IRB)
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。