The CARDIOPROTECT Trial
2026年7月24日 更新者：Jenica Upshaw、Beth Israel Deaconess Medical Center
A Randomized Study of Dexrazoxane or Liposomal Doxorubicin in Newly Diagnosed Diffuse Large B-cell Lymphoma at High Risk for Heart Failure Events: the CARDIOPROTECT Trial
This trial is to evaluate if dexrazoxane is safer and more effective than liposomal doxorubicin in preventing heart failure events in participants with diffuse large B-cell lymphoma (DLBCL) undergoing either standard of care R-CHOP or pola-R-CHP treatment regiments.
The names of the study drugs involved in this study are:
- Dexrazoxane (a type of Topoisomerase II Inhibitor)
- Liposomal Doxorubicin (a type of Topoisomerase II Inhibitor)
- Standard of care R-CHOP treatment regimen (Cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab)
- Standard of care pola-R-CHP treatment regimen: Cyclophosphamide, doxorubicin, polatuzumab vedotin-piiq, prednisone, rituximab
調査の概要
状態
募集
詳細な説明
This phase II, multicenter, randomized, double-blind, double-dummy trial is to evaluate if dexrazoxane is safer and more effective than liposomal doxorubicin in preventing heart failure events in participants with diffuse large B-cell lymphoma (DLBCL) undergoing either standard of care R-CHOP or pola-R-CHP treatment regiments.
Participants will be assigned by the study doctor to standard of care R-CHOP or standard of care pola-R-CHP therapy regimens.
R-CHOP Participants will be randomized into 1 of 2 study groups: Group A: Dexrazoxane, cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab versus Group B: Placebo, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone, rituximab. Participants will have an equal chance of being placed into one of those study groups.
Pola-R-CHP participants will be randomized into 1 of 2 study groups: Group C: Dexrazoxane, cyclophosphamide, doxorubicin, polatuzumab vedotin-piiq, prednisone, rituximab versus Group D: Placebo, cyclophosphamide, liposomal doxorubicin, polatuzumab vedotin-piiq, prednisone, rituximab. Participants will have an equal chance of being placed into one of those study groups.
Randomization means a participant is placed into a study group by chance. Neither a participant or the study doctor will choose or know what group a participant is placed in. This is called a "double-blind" study.
The research study procedures include screening for eligibility, in-clinic visits, questionnaires, blood tests, urine tests, electrocardiograms (ECGs), and echocardiograms (ECHO).
The U.S. Food and Drug Administration (FDA) has not approved dexrazoxane for DLBCL.
The FDA has not approved liposomal doxorubicin for DLBCL. The FDA has approved all the drugs in R-CHOP as a treatment option for DLBCL. The FDA has approved all the drugs in pola-R-CHP as a treatment option for DLBCL It is expected that about 60 people will take part in this research study. The National Cancer Institute is sponsoring this study by providing funding.
研究の種類
介入
入学 (推定)
60
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Jenica Upshaw, MD, MSc
- 電話番号：(617) 667-8800
- メール：jupshaw@bidmc.harvard.edu
研究場所
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02215
- 募集
- Beth Israel Deaconess Medical Center
-
コンタクト：
- Jenica Upshaw, MD, MSc
- 電話番号：(617) 667-8800
- メール：jupshaw@bidmc.harvard.edu
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
- Participants must have histologically confirmed diffuse large B-cell lymphoma, histologically transformed large B cell lymphoma from a prior indolent lymphoma, or other high-grade B-cell lymphoma for which R-CHOP or pola-R-CHP are planned. Any cancer stage is permitted.
- Participants must not have received any prior chemotherapy for this malignancy. Pre-phase steroids are allowed. Prior treatment for a different malignancy is allowed, including prior treatment for indolent lymphoma.
- Age ≥18 years. Diffuse large B cell lymphoma is rare in participants <18 years of age. The prevalence of HF prior to chemotherapy is also exceedingly rare in participants <18 years of age; therefore, participants <18 years of age are excluded from this study.
Participants must have ONE or more of the following risk factors for HF events with anthracycline-containing chemotherapy
- LVEF 30-50% on most recent echocardiogram with or without HF history
- LVEF 50% with a history of HF (i.e. HF with improved EF or HF with preserved EF).
- History of anthracycline exposure for different malignancy.
- Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Because dexrazoxane as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of chemotherapy administration.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- New York Heart Association (NYHA) Class III or IV exertional dyspnea. The symptoms should be attributed to HF and not due to lymphoma, anemia, arthritis or other causes per the assessment of the treating clinician or study investigator. NYHA Class III defined as: "Marked limitations with less than ordinary activity such as walking short distances or climbing a few stairs" and NYHA Class IV defined as: "Inability to carry out any activity without discomfort. Symptoms are present at rest and if any physical activity is undertaken the symptoms are increased." (see Appendix A for NYHA Classification).
- LVEF <30% on most recent echocardiogram. Patients with prior LVEF <30% with improvement to >30% on most recent echocardiogram are eligible.
- Meeting criteria for frailty according to the simplified geriatric assessment (see Appendix A for the simplified geriatric assessment criteria).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in study.
- Presence of central nervous system involvement
- Presence of concurrent genetic rearrangements of the MYC and BCL2 genes, so called "double-hit" large-cell lymphoma who are not deemed eligible for intensified induction chemotherapy such as dose adjusted EPOCH-R by their treating physician can be enrolled
- Ineligible for R-CHOP or pola-R-CHP because of liver disease per institutional policies
- Patients with planned dose reductions from the first cycle ie R-mini-CHOP will be excluded
- There are no contraindicated medications. Caution and monitoring are advised with medications that can cause myelosuppression.
- Patients with positive Hepatitis B core antibody can be enrolled if they have negative viral load and can be maintained on antiviral prophylaxis
- Patients with HIV can be enrolled if they have anti-retroviral therapy options without drug-drug interactions with the cancer treatment, agree to take anti-retroviral therapy and do not have uncontrolled opportunistic infections.
- Pregnant women are excluded from this study because dexrazoxane and liposomal doxorubicin are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with dexrazoxane and liposomal doxorubicin, breastfeeding should be discontinued if the mother is treated with dexrazoxane and liposomal doxorubicin. These potential risks may also apply to other agents used in this study.
- Eligibility for observational arm of the study. The above inclusion and exclusion criteria are for the randomized trial. Patients who meet the inclusion criteria but have one or more exclusion criterion are eligible to participate in the observational arm of the study. In addition, patients who meet all eligibility criteria for the randomized trial but decline participation in the randomized trial are also eligible to participate in the observational arm of the study.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Arm A: Dexrazoxane + Doxorubicin + RCHOP
Participants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete:
|
Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
他の名前：
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
他の名前：
vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
他の名前：
Glucocorticoid, tablet taken orally per standard of care.
他の名前：
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
他の名前：
|
|
プラセボコンパレーター：Arm B: Dexrazoxane Placebo + Liposomal Doxorubicin + RCHOP
Participants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete:
|
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
他の名前：
vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
他の名前：
Glucocorticoid, tablet taken orally per standard of care.
他の名前：
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
他の名前：
Dexrazoxane placebo via intravenous infusion per protocol.
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
|
|
実験的：Arm C: Dexrazoxane + Doxorubicin + pola-R-CHP
Participants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete: Baseline visit
|
Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
他の名前：
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
他の名前：
Glucocorticoid, tablet taken orally per standard of care.
他の名前：
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
他の名前：
CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
他の名前：
|
|
プラセボコンパレーター：Arm D: Dexrazoxane Placebo + Liposomal Doxorubicin + pola-R-CHP
Participants will be randomized in 1:1 ratio and stratified by cancer stage and enrolling site to this group and will complete:
|
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
他の名前：
Glucocorticoid, tablet taken orally per standard of care.
他の名前：
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
他の名前：
Dexrazoxane placebo via intravenous infusion per protocol.
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
他の名前：
|
|
他の：Arm E: Observational R-CHOP
Participants meeting inclusion but not all exclusion criteria, or who decline randomization, may enroll in an observational cohort for data and biospecimen collection and will complete the following:
|
Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
他の名前：
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
他の名前：
vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
他の名前：
Glucocorticoid, tablet taken orally per standard of care.
他の名前：
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
他の名前：
Dexrazoxane placebo via intravenous infusion per protocol.
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
|
|
他の：Arm F: Observational pola-R-CHP
Participants meeting inclusion but not all exclusion criteria, or who decline randomization, may enroll in an observational cohort for data and biospecimen collection and will complete the following:
|
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
他の名前：
Glucocorticoid, tablet taken orally per standard of care.
他の名前：
Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
他の名前：
Dexrazoxane placebo via intravenous infusion per protocol.
Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
他の名前：
CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
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 |
|---|---|---|
|
Left Ventricular Ejection Fraction (LVEF)
時間枠：LVEF will be assessed by echocardiography 3 months after completion of front-line chemotherapy, with chemotherapy administered for up to 18 weeks.
|
LVEF represents the proportion of blood ejected from the left ventricle during each heartbeat and is calculated as LVEF=(ECV-ESV)/EDV, where EDV is the end-diastolic volume (the volume of blood in the ventricle at the end of filling) and ESV is the end-systolic volume (the volume of blood remaining in the ventricle after contraction).
|
LVEF will be assessed by echocardiography 3 months after completion of front-line chemotherapy, with chemotherapy administered for up to 18 weeks.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Time to First Heart Failure (HF) Events
時間枠：Up to 5 years
|
Time to first HF events is defined as the time from randomization to the first adjudicated heart failure event, including HF-related hospitalizations, emergency department visits, or urgent outpatient visits for worsening HF, or censoring at last follow-up, study withdrawal, based on a cause-specific hazard model.
|
Up to 5 years
|
|
Time to Recurrent Heart Failure (HF) Events
時間枠：Up to 5 years
|
Time to recurrent HF events is defined as the time from randomization to all adjudicated heart failure event, including HF-related hospitalizations, emergency department visits, or urgent outpatient visits for worsening HF, or censoring at last follow-up, study withdrawal, based on Andersen-Gill or Lin-Wei-Ying-Yang (LWYY) models.
|
Up to 5 years
|
|
Changes in 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Score from Baseline
時間枠：Health status will be assessed at baseline, at cycle 3 of chemotherapy, at 3 and 12 months post-chemotherapy, and annually through 5 years, with chemotherapy administered for up to 18 weeks.
|
This endpoint evaluates score changes in self-reported health status using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which ranges from 0 to 70, with higher scores indicating better health status.
Clinically meaningful changes are defined as 5-, 10-, and 20-point thresholds.
|
Health status will be assessed at baseline, at cycle 3 of chemotherapy, at 3 and 12 months post-chemotherapy, and annually through 5 years, with chemotherapy administered for up to 18 weeks.
|
|
Changes in Patient-Reported Outcomes Measurement Information System 10-Item Global Health Scale (PROMIS-10) Score from Baseline
時間枠：Health status will be assessed at baseline, at cycle 3 of chemotherapy, at 3 and 12 months post-chemotherapy, and annually through 5 years, with chemotherapy administered for up to 18 weeks.
|
This endpoint evaluates changes in self-reported global health status using the 10-item PROMIS Global scale (PROMIS-10), in which the first 9 items are scored 1-5 and the last item is scored 0-10, with higher scores indicating better overall physical and mental health.
|
Health status will be assessed at baseline, at cycle 3 of chemotherapy, at 3 and 12 months post-chemotherapy, and annually through 5 years, with chemotherapy administered for up to 18 weeks.
|
|
Change in N-terminal pro-B-type Natriuretic Peptide (NT-proBNP)
時間枠：Biomarkers will be measured at baseline prior to chemotherapy, every 2 cycles during chemotherapy, and at 3 and 12 months post-chemotherapy to assess treatment-related changes over time, with chemotherapy administered for up to 18 weeks.
|
NT-proBNP is measured in picograms per milliliter (pg/mL) using established laboratory methods.
Values are collected to assess changes in neurohormonal activation.
|
Biomarkers will be measured at baseline prior to chemotherapy, every 2 cycles during chemotherapy, and at 3 and 12 months post-chemotherapy to assess treatment-related changes over time, with chemotherapy administered for up to 18 weeks.
|
|
Change in High-Sensitivity Troponin
時間枠：Biomarkers will be measured at baseline prior to chemotherapy, every 2 cycles during chemotherapy, and at 3 and 12 months post-chemotherapy to assess treatment-related changes over time, with chemotherapy administered for up to 18 weeks.
|
High-sensitivity troponin is measured in nanograms per liter (ng/L) using established
|
Biomarkers will be measured at baseline prior to chemotherapy, every 2 cycles during chemotherapy, and at 3 and 12 months post-chemotherapy to assess treatment-related changes over time, with chemotherapy administered for up to 18 weeks.
|
|
Median Progression-Free Survival (PFS)
時間枠：Up to 5 years
|
PFS based on Kaplan-Meier method is defined as from date of registration to date of first observation of progressive disease according to the 2014 Lugano classification, or death due to any cause.
Participants last known to be alive and without report of progression are censored at date of last contact.
|
Up to 5 years
|
|
Time to First Cardiovascular (CV) Event
時間枠：Up to 5 years
|
Time to first CV event is defined as the time from randomization to the first adjudicated major cardiovascular event, including acute coronary syndrome, ischemic or hemorrhagic stroke, atrial fibrillation or atrial flutter, or ventricular tachycardia, with death treated as a competing risk.
|
Up to 5 years
|
|
Median Overall Survival (OS)
時間枠：Up to 5 years
|
OS based on Kaplan-Meier method is defined as the time from randomization (or registration) to death due to any cause or censored at date last known alive.
|
Up to 5 years
|
|
Cause-Specific Mortality
時間枠：Up to 5 years
|
Cause-specific mortality will be analyzed using a cause-specific proportional hazards model, with deaths from other causes treated as competing risks, to estimate the relative effect of treatment on cause-specific mortality.
|
Up to 5 years
|
|
Grade 2 or Higher Adverse Event (AE) Rate
時間枠：Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.
|
Grade 2 or higher AE rate is defined as the proportion of participants who experience grade 2 or higher AE.
AE will be summarized and graded based on CTCAE 5.0.
|
Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.
|
|
Grade 3 or Higher Adverse Event (AE) Rate
時間枠：Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.
|
Grade 3 or higher AE rate is defined as the proportion of participants who experience grade 3 or higher AE.
AE will be summarized and graded based on CTCAE 5.0.
|
Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Jenica Upshaw, MD, MSc、Beth Israel Deaconess Medical Center
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年8月31日
一次修了 (推定)
2030年12月31日
研究の完了 (推定)
2035年12月31日
試験登録日
最初に提出
2026年6月12日
QC基準を満たした最初の提出物
2026年6月12日
最初の投稿 (実際)
2026年6月17日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月27日
QC基準を満たした最後の更新が送信されました
2026年7月24日
最終確認日
2026年7月1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
- 傷やけが
- 病理学的プロセス
- 新生物
- 心臓疾患
- 免疫系疾患
- 組織型別の新生物
- 化学誘発性疾患
- リンパ疾患
- リンパ増殖性疾患
- 免疫増殖性疾患
- リンパ腫、非ホジキン
- リンパ腫、B細胞
- 薬物関連の副作用と有害反応
- 放射線障害
- 病理学的状態、徴候および症状
- ヘミックおよびリンパ疾患
- リンパ腫
- リンパ腫、大型B細胞、びまん性
- 心毒性
- アミノ酸、ペプチド、およびタンパク質
- タンパク質
- 有機化学物質
- 複素環化化合物、1リング
- 複素環化化合物
- 複素環化化合物、2リング
- 複素環化化合物、融合リング
- 炭化水素
- 炭化水素、周期的
- 炭水化物
- アルカロイド
- 多環芳香族炭化水素
- 炭化水素、芳香
- 多環式化合物
- グリコシド
- インドール
- 抗体、モノクローナル
- 抗体
- 免疫グロブリン
- 免疫タンパク質
- 血液タンパク質
- 血清グロブリン
- グロブリン
- 妊娠
- 妊娠
- ステロイド
- 融合リング化合物
- ホスホルアミドマスタード
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- ホスホラミド
- 有機リン化合物
- 妊娠した
- ヴィンカアルカロイド
- セコロガニントリプタミンアルカロイド
- インドールアルカロイド
- インドリジジン
- インドリジン
- アントラサイクリン
- ナフテセン
- アミノグリコシド
- 抗体、モノクローナル、マウス由来
- ダウノルビシン
- ピペラジン
- ラゾキサン
- ディケットピペラジン
- リツキシマブ
- プレドニン
- シクロホスファミド
- ドキソルビシン
- ビンクリスチン
- デクスラゾキサン
- ポラツマブヴェドチン
- リポソームドキソルビシン
- 1-ドデシルピリドキサル
その他の研究ID番号
- 25-814
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
The Harvard Cancer Consortium encourages and supports the responsible and ethical sharing of data from clinical trials.
De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement.
Requests may be directed to: [contact information for Sponsor Investigator or designee].
The protocol and statistical analysis plan will be made available on Clinicaltrials.gov
only as required by federal regulation or as a condition of awards and agreements supporting the research.
IPD 共有時間枠
Data can be shared no earlier than 1 year following the date of publication
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
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
はい
米国FDA規制機器製品の研究
いいえ
米国で製造され、米国から輸出された製品。
いいえ
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。