Yttrium Y 90 Anti-CD45 Monoclonal Antibody AHN-12 in Treating Patients With Advanced Leukemia
MT2005-13R - Phase I Open Label, Single Arm, Dose Escalation Trial to Evaluate the Biodistribution and Safety of AHN-12 in Patients With Advanced Leukemia
RATIONALE: Monoclonal antibodies can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Radioactive monoclonal antibodies, such as yttrium Y 90 monoclonal antibody, can find cancer cells and either kill them or carry cancer-killing substances to them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of a yttrium Y 90 monoclonal antibody and how much radiation is taken in by the organs in the body in treating patients with advanced leukemia or other hematologic disorder.
調査の概要
状態
詳細な説明
OBJECTIVES:
Primary
- To establish that a dose of 150 mg/m² of nonradiolabeled anti-CD45 monoclonal antibody AHN-12 results in normal biodistribution, normal-organ estimated radiation-absorbed dose of less than 20 Gy, and estimated radiation-absorbed dose of no more than 13 Gy to the red marrow.
Secondary
- To determine the maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (^90Y-AHN-12).
- To determine the human anti-mouse antibody (HAMA) response.
- To define, preliminarily, the antitumor activity of ^90Y-AHN-12.
OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (^90Y-AHN-12).
- Biodistribution: Patients receive nonradiolabeled monoclonal antibody AHN-12 IV and an imaging dose of indium Y 111 monoclonal antibody AHN-12 (^111In-AHN-12) IV over 10 minutes on day 0. Patients undergo whole-body gamma-camera imaging immediately following infusion, at 4-6 hours, and on days 1, 3, 4, and 7. Blood samples are collected prior to each imaging for dosimetry calculations and pharmacokinetics.
Patients also undergo bone marrow biopsy 16-24 hours after infusion for dosimetry calculations. Patients with the expected biodistribution of ^111In-AHN-12, an estimated radiation-absorbed dose to the normal organ of < 20 Gy, an estimated radiation-absorbed dose to the red marrow of ≤ 13 Gy, and a negative human anti-mouse antibody at day 7 proceed to the therapy portion.
- Treatment: Patients receive nonradiolabeled anti-CD45 monoclonal antibody AHN-12 IV over 60 minutes and escalating therapy doses of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12 (^90Y-AHN-12) IV over 10 minutes on day 7 or 8.
After completion of study treatment, patients are followed periodically for 1 year.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Minnesota
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Minneapolis、Minnesota、アメリカ、55455
- Masonic Cancer Center at University of Minnesota
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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
Inclusion Criteria:
Histologically confirmed CD45+ diseases:
Acute lymphoblastic leukemia or acute myeloid leukemia (AML), meeting any of the following criteria:
- Primary refractory disease
- Relapsed disease, defined as persistent disease following a minimum of 2 different standard chemotherapy induction attempts at time of diagnosis or at relapse
- Acute myelogenous leukemia (AML), primary refractory or relapsed disease - defined as persistent disease after a minimum of two different standard chemotherapy induction attempts at time of diagnosis or relapse
- Advanced myelodysplastic syndrome (MDS) defined as > or = 15% bone marrow blasts following a minimum of one standard chemotherapy induction attempt
- AML arising from preexisting MDS, refractory - defined as persistent disease following a minimum of one standard chemotherapy induction attempt
- Chronic myelogenous leukemia (CML) following blast crisis (> or = 15% marrow blasts following a minimum of one standard chemotherapy induction attempt
- Peripheral leukemic blasts (by morphology) must be < 5,000/μL (hydroxyurea to control peripheral blast count allowed)
- Must have source of allogeneic stem cells (sibling, unrelated cord[s], or donor) identified prior to initiation of protocol therapy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS 60-100%
- Life expectancy > 12 weeks
- Total bilirubin ≤ 2.5 times upper limit of normal (ULN)
- aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN)
- Creatinine ≤ 1.3 mg/dL OR creatinine clearance ≥ 60 mL/min
- Left ventricular ejection fraction (LVEF) ≥ 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram (ECHO)
- Carbon Monoxide Diffusing Capacity (DLCO) (corrected) ≥ 50% of predicted
- Human anti-mouse antibody (HAMA) must be negative
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Human immunodeficiency virus (HIV) negative
- Recovered from all prior therapy
- At least 7 days since prior biologic agents
Exclusion Criteria:
- Bone marrow cellularity < 15%
- Known brain metastases or active central nervous system (CNS) disease
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ^90Y-AHN-12 or other agents used in study
Uncontrolled illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic or congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
- Other concurrent investigational agents
- Prior allogeneic transplantation
- Less than 60 days since prior autologous transplantation with relapsed disease
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：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：AHN-12
2.0, 5.0, 7.5, 10.0 or 12.5 mCi/m^2 of ^90Y-AHN-12 at Day 7/8
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150 mg/m^2 cold antibody at Day 0
他の名前：
Dose per scheduled level; 2.5-12.5 mCi/m^2
他の名前：
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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 |
時間枠 |
|---|---|
|
Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12
時間枠：Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
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Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody AHN-12
時間枠：Week 8
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Week 8
|
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Presence of human antibody to murine antibody
時間枠：at baseline and at 28 days, 90 days, and 6 months after completion of study treatment
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at baseline and at 28 days, 90 days, and 6 months after completion of study treatment
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Dose-limiting toxicity and response
時間枠：at days 28 and 90 after completion of study treatment
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at days 28 and 90 after completion of study treatment
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協力者と研究者
捜査官
- 主任研究者：Linda J. Burns, MD、Masonic Cancer Center, University of Minnesota
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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2005LS039
- UMN-MT2005-13R (その他の識別子：Blood and Marrow Transplantation Program)
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