High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant
A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVES:
I. To determine time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20X 109^/L for 3 consecutive days).
2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).
3. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).
SECONDARY OBJECTIVES:
I. Incidence of myeloma progression in this high risk group of patients.
II. Incidence of transplant related mortality and morbidity.
III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).
IV. Incidence and severity of chronic GVHD.
V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.
I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post transplant.
VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.
OUTLINE:
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.
GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.
After completion of study treatment, patients are followed up for up to 2 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
-
-
Michigan
-
Detroit、Michigan、アメリカ、48201
- Barbara Ann Karmanos Cancer Institute
-
-
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
Inclusion Criteria:
- Ability to provide informed consent
- Karnofsky Performance Status (KPS) >= 70
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor
- High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria:
- Progressive disease after autologous transplant. No less than 3 months post auto transplant
- Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib
- Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics
- Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women
Exclusion Criteria:
- Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason
- Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason
- Patient with history of allergy to boron, mannitol, or bortezomib
- Creatinine clearance (CrCl) =< 50 ml/min
- Ejection Fraction < 50%
- Diffusion capacity of carbon monoxide (DLCO) < 50% predicted
- Forced expiratory volume in 1 second (FEV1) < 50% predicted
- Forced vital capacity (FVC) < 50% predicted
- Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator
- Liver enzymes > 3 times upper limit normal
- Bilirubin > 2 mg/dl (except Gilbert's disease)
- International normalized ratio (INR) > 2
- Any previous history of liver failure, hepatitis, or cirrhosis
- Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection
- Grade > I neuropathy
- Women who are pregnant or lactating
- Current or history of alcohol or drug abuse
- Use of other investigational agents within 30 days of enrollment to this study
- Any patient with ascites
- Any patient on home oxygen
- Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study
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：Treatment (chemotherapy, enzyme inhibitor)
CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0. |
相関研究
与えられた IV
他の名前：
相関研究
他の名前：
与えられた IV
他の名前：
与えられたPO
他の名前：
与えられた IV
他の名前：
与えられた IV
他の名前：
同種HSCTを受ける
与えられた IV
他の名前：
|
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 |
|---|---|---|
|
Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
時間枠：First 6 months post-transplant
|
Graded using the Glucksberg scale.
Proportions and confidence intervals will be estimated.
Estimated using binary proportion estimates as well as competing risk method.
|
First 6 months post-transplant
|
|
Time to Platelet Absolute Neutrophil Recovery (Engraftment)
時間枠：First 6 months post-transplant
|
Estimated using Kaplan-Meier method.
|
First 6 months post-transplant
|
|
Treatment Related Mortality Defined as Death in Continuous or Complete Remission
時間枠：From the date of transplant to the date of death, assessed up to 6 months post transplant
|
Based on National Cancer Institute (NCI) CTCAE version 4.
|
From the date of transplant to the date of death, assessed up to 6 months post transplant
|
|
Grade III and IV Non Hematologic Toxicities
時間枠：First 6 months post transplant
|
Based on NCI CTCAE version 4.
|
First 6 months post transplant
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
全生存
時間枠：移植後2年まで
|
移植後2年まで
|
|
Incidence of Myeloma Progression
時間枠：Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
|
Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
|
|
Incidence of Transplant Related Mortality and Morbidity
時間枠：Up to 2 years post transplant
|
Up to 2 years post transplant
|
|
Incidence of TTP
時間枠：Up to 2 years post transplant
|
Up to 2 years post transplant
|
|
Incidence of SOS
時間枠：Up to 2 years post transplant
|
Up to 2 years post transplant
|
|
Incidence and Severity of Chronic GVHD
時間枠：Up to 2 years post transplant
|
Up to 2 years post transplant
|
|
Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation
時間枠：Weekly to day 100
|
Weekly to day 100
|
|
Progression Free Survival
時間枠：From the day of transplant to progression, death, or last contact, assessed up to 2 years
|
From the day of transplant to progression, death, or last contact, assessed up to 2 years
|
|
Recovery of T-cell, B Cell and NK Cell Phenotypes
時間枠：Days 30, 60, 90, and at 6 months after transplant
|
Days 30, 60, 90, and at 6 months after transplant
|
協力者と研究者
捜査官
- 主任研究者：Zaid Al-Kadhimi、Barbara Ann Karmanos Cancer Institute
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 (実際)
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
追加の関連 MeSH 用語
その他の研究ID番号
- 2011-151
- NCI-2012-00120 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
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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