Everolimus, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Untreated Diffuse Large B-Cell Lymphoma
A Phase I and Feasibility Study of Everolimus (RAD001) Plus R-CHOP for New Untreated Diffuse Large B-Cell Lymphoma (DLBCL)
RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer cells in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Giving everolimus together with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and the best dose of everolimus when given together with rituximab and combination chemotherapy in treating patients with newly diagnosed untreated diffuse large B-cell lymphoma.
調査の概要
状態
条件
詳細な説明
OBJECTIVES:
Primary
- To establish the maximum-tolerated dose (MTD) of everolimus in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone) chemotherapy.
- To assess the feasibility of everolimus in combination with standard R-CHOP chemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma.
Secondary
- To describe the toxicities associated with everolimus in combination with R-CHOP chemotherapy.
- To further describe the toxicities associated with everolimus in combination with R-CHOP chemotherapy.
- To assess the rate of event-free survival (EFS) at 12 months for diffuse large B-cell lymphoma patients treated with everolimus in combination with R-CHOP chemotherapy.
- To evaluate overall response rate, complete response rate, duration of response, EFS, overall survival, and progression-free survival for patients treated with everolimus in combination with R-CHOP chemotherapy.
Tertiary
- To profile gene expression using immunohistochemistry and categorize patients as germinal-center B-cell-like (GBC) vs activated B-cell-like (ABC) vs unclassified lymphoma subtype. (exploratory)
- To determine whether previously identified predictive markers in large cell lymphoma remain valid with the addition of everolimus to R-CHOP chemotherapy. (exploratory)
OUTLINE: This is a multicenter, dose-escalation study of everolimus followed by a feasability expanded-cohort study.
Patients receive everolimus orally (PO) once daily (QD) on days 1-10 or 1-14; rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV over 15-60 minutes, and vincristine sulfate IV on day 1; and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Tumor biopsies are collected for laboratory studies and patients may undergo blood and needle biopsy sample collection for correlative studies.
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
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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Rochester、Minnesota、アメリカ、55905
- Mayo Clinic Cancer Center
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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:
- Untreated, histological diagnosis of CD20-positive diffuse large B-cell lymphoma
- Stage II-IV (Ann Arbor Staging)
Measurable or assessable disease defined as at least one of the following:
- A lymph node or tumor mass that is ≥ 2.0 cm in at least one dimension by CT portion of PET/CT scan, CT scan, or MRI
- Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease
- Diagnostic tissue slides and paraffin-embedded block must be available
- No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count (ANC) ≥ 1,500/mm³
- Peripheral platelet count ≥ 100,000/mm³
- Hemoglobin (HgB) > 9.0 g/dL
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- For total bilirubin > 1.5 times ULN, the direct bilirubin must be normal
- Alkaline phosphatase ≤ 3 times ULN (≤ 5 times ULN if evidence of direct liver involvement by lymphoma)
- AST ≤ 3 times ULN (≤ 5 times ULN if evidence of direct liver involvement by lymphoma)
- Creatinine ≤ ULN
- Negative serum or urine pregnancy test
- Not pregnant or nursing
- Men or women of childbearing potential must be willing to employ adequate contraception throughout the study and for12 months after the last dose of study drug
- Willing to return to the National Central Cancer Treatment Group (NCCTG) enrolling institution for follow-up
- Willing to provide archival tissue from the primary diagnosis (original lymphoma lymph node tissue biopsy)
- Willing to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
- Diabetic patients who are taking insulin or oral anti-diabetic therapy must have HbA1c ≤ 8%, or a fasting serum glucose ≤ 110% ULN
- HIV-positive patients must have CD4 count ≥ 400/mm³
- No co-morbid systemic illnesses or other severe concurrent disease that, 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
- No immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be HIV positive with a CD4 count of < 400/mm³
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Severely impaired lung function
Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN
- Optimal glycemic control should be achieved before starting trial therapy
- Psychiatric illness/social situations that would limit compliance with study requirements
- Liver disease such as cirrhosis or severe hepatic impairment
- Chronic active hepatitis
- Chronic persistent hepatitis or history of hepatitis B or C
No other active malignancy except non-melanotic skin cancer or carcinoma in situ of the cervix
- If there is a history of prior malignancy, patients must not be receiving other specific treatment (other than hormonal therapy) for their cancer
No positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests meeting the following criteria:
- Hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core (anti-HBc) or hepatitis C antibody
- All patients must be screened prior to registration
- Patients who have evidence of chronic or acute infection with either hepatitis B or C may not be treated on this protocol
PRIOR CONCURRENT THERAPY:
- Not receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
No planned immunization with attenuated live vaccines ≤ 7 days prior to registration or during study period
- Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus
- Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines
- Not currently on enzyme-inducing anti-convulsants or other strong inducers of CYP3A4 (efavirenz, nevirapine, barbiturates, carbamazepine, modafinil, phenobarbital, phenytoin, rifabutin, rifampin, pioglitazone, or St. John wort) or strong inhibitors of CYP3A4 (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, saquinavir, or telithromycin)
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 |
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実験的:everolimus and RCHOP
Patients registered to the study will receive an assigned dose of everolimus by mouth and RCHOP for a maximum of six cycles.
Each cycle is a total of 21 days.
RCHOP consists of 375 mg/m2 IV rituximab, 750 mg/m2 IV cyclophosphamide, 50 mg/m2 IV doxorubicin, 1.4 mg/m2 IV vincristine and 100 mg/m2 by mouth QD prednisone.
The study includes a Phase I component to determine the maximum tolerated dose of everolimus and the second component determines the feasibility of therapy administered to lymphoma patients.
|
Ⅳ
Ⅳ
PO
IV
PO
PO
|
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 |
---|---|
MTD of everolimus in combination with R-CHOP
時間枠:Up to 15 months post registration to Phase I portion of the study
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Up to 15 months post registration to Phase I portion of the study
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Adverse events profile
時間枠:Up to 15 months post registration to Phase I portion of the study
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Up to 15 months post registration to Phase I portion of the study
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Toxicity profile
時間枠:Up to 15 months post registration to Phase I portion of the study
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Up to 15 months post registration to Phase I portion of the study
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Proportion of patients who have a significant toxicity
時間枠:Up to 2.5 years post registration to Feasibility portion of the study
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Up to 2.5 years post registration to Feasibility portion of the study
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二次結果の測定
結果測定 |
時間枠 |
---|---|
Rate of EFS
時間枠:Up to 5 years post treatment of the feasibility portion of the study
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Up to 5 years post treatment of the feasibility portion of the study
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Overall response rate, CR rate, overall survival, PFS, and duration of response
時間枠:Up to 5 years post treatment of the feasibility portion of the study
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Up to 5 years post treatment of the feasibility portion of the study
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協力者と研究者
捜査官
- スタディチェア:Patrick Johnston, MD, PhD、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 (実際)
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
- 免疫系疾患
- 組織型別の新生物
- 新生物
- リンパ増殖性疾患
- リンパ疾患
- 免疫増殖性疾患
- リンパ腫、非ホジキン
- リンパ腫、B細胞
- リンパ腫
- リンパ腫、大型B細胞、びまん性
- 薬の生理作用
- 薬理作用の分子機構
- 酵素阻害剤
- 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
- チューブリンモジュレーター
- 抗有糸分裂剤
- 有糸分裂モジュレーター
- 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
- 抗悪性腫瘍剤、ファイトジェニック
- トポイソメラーゼ II 阻害剤
- トポイソメラーゼ阻害剤
- 抗悪性腫瘍剤、免疫
- 抗生物質、抗悪性腫瘍薬
- シクロホスファミド
- リツキシマブ
- プレドニゾン
- ドキソルビシン
- リポソームドキソルビシン
- ビンクリスチン
- エベロリムス
その他の研究ID番号
- NCCTG-N1085
- CDR0000698584 (レジストリ識別子:PDQ (Physician Data Query))
- NCI-2011-02643 (レジストリ識別子:CTRP (Clinical Trials Reporting System))
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。