Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis
Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)
RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis.
PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Compare hematologic response rate in patients with primary systemic amyloidosis treated with conventional chemotherapy comprising low-dose melphalan and dexamethasone vs high-dose melphalan followed by autologous stem cell transplantation.
- Compare the toxicity of these regimens in these patients.
Secondary
- Compare the overall and progression-free survival of patients treated with these regimens.
- Compare the regression of organ involvement in patients treated with these regimens.
- Compare the duration of response in patients treated with these regimens.
- Correlate clonal burden and time to in vitro amyloid formation with clinical outcomes in patients treated with these regimens.
- Compare quality of life of patients treated with these regimens.
- Compare the information-seeking behavior in patients treated with these regimens.
OUTLINE: This is a comprehensive cohort study comprising a randomized option and a nonrandomized option. Patients consenting to randomization are stratified by risk group (high vs low) and ECOG performance status (0-1 vs 2). They are then randomized to 1 of 2 treatment arms. Patients not consenting to randomization choose their treatment arm.
- Arm I: Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
Blood and bone marrow samples are collected at baseline. Samples are examined by PCR, cDNA, and nucleotide sequence analysis to determine VH and VL gene families and carrier status. Urine is collected at baseline and analyzed for light-chain protein levels by exclusion chromatography.
Quality of life is assessed at baseline, at months 3, 9, and 12, at completion of study treatment, and then every 6 months for up to 5 years.
After completion of study treatment, patients are followed every 6 months for up to 10 years.
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
-
-
Minnesota
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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic
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-
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:
Histologically confirmed primary systemic amyloidosis
- Amyloid light-chain (AL) disease
- Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine OR abnormal free light-chain ratio
The following amyloid syndromes* are allowed:
- Amyloid hepatomegaly
- Cardiomyopathy
- Proteinuria
- Peripheral or autonomic neuropathy
- Soft tissue involvement including the tongue, submandibular tissues, and vascular claudication
- Diffuse interstitial pulmonary AL disease allowed if pulmonary function is adequate to allow safe transplantation NOTE: *Presence of amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic patient does not constitute an amyloid syndrome
- No secondary or familial amyloidosis
- No multiple myeloma with lytic or destructive bone lesions or myeloma cast nephropathy
- No multiple myeloma with > 30% plasma cells in the bone marrow
- No amyloidosis manifested only by carpal tunnel syndrome or purpura
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 2.0 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 6 times ULN
- Creatinine ≤ 3.0 mg/dL
- No NYHA class IV heart disease
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No uncontrolled infection
- No HIV positivity
PRIOR CONCURRENT THERAPY:
Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they were given for < 1 month
- Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at discretion of physician
- No concurrent participation in another clinical trial involving a pharmacologic agent
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：非ランダム化
- 介入モデル：並列代入
- 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 |
|---|---|
|
アクティブコンパレータ：Arm A
Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses. Study treatment beyond one year is not allowed. |
経口投与
Given IV or orally
|
|
実験的：Arm B
Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection.
Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
|
Given IV or orally
No administration information given
0日目に付与
|
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 |
|---|---|---|
|
Hematologic Response Rate
時間枠：10 years
|
Response that was confirmed on 2 consecutive evaluations during treatment. A hematologic response consisted of a Complete response, Very Good Partial Response or Partial Response.
|
10 years
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
3 Year Overall Survival
時間枠：3 years
|
Percentage of patients who were alive at 3 years.
The 3-year survival rate was estimated using the Kaplan Meier method.
|
3 years
|
|
Organ Response to Treatment
時間枠：10 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%. |
10 years
|
協力者と研究者
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
- デキサメタゾン
- メルファラン
その他の研究ID番号
- CDR0000546745
- P30CA015083 (米国 NIH グラント/契約)
- MC0482 (その他の識別子：Mayo Clinic Cancer Center)
- 1691-05 (その他の識別子：Mayo Clinic IRB)
- NCI-2009-01329 (レジストリ識別子：NCI-CTRP)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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。
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