The CARDIOPROTECT Trial

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Dexrazoxane
  Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
• Препарат Dexrazoxane placebo
  Dexrazoxane placebo via intravenous infusion per protocol.
• Препарат Doxorubicin
  Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
• Препарат Liposomal Doxorubicin
  Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
• Препарат Cyclophosphamide
  Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
• Препарат Vincristine
  vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
• Препарат Prednisone
  Glucocorticoid, tablet taken orally per standard of care.
• Препарат Rituximab
  Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
• Препарат Polatuzumab Vedotin
  CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.

Первичные конечные точки

• Left Ventricular Ejection Fraction (LVEF) [Срок оценки: LVEF will be assessed by echocardiography 3 months after completion of front-line chemotherapy, with chemotherapy administered for up to 18 weeks.]

Вторичные конечные точки (12)

• Time to First Heart Failure (HF) Events [Срок оценки: Up to 5 years]
• Time to Recurrent Heart Failure (HF) Events [Срок оценки: Up to 5 years]
• Changes in 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Score from Baseline [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: Up to 5 years]
• Time to First Cardiovascular (CV) Event [Срок оценки: Up to 5 years]
• Median Overall Survival (OS) [Срок оценки: Up to 5 years]
• Cause-Specific Mortality [Срок оценки: Up to 5 years]
• Grade 2 or Higher Adverse Event (AE) Rate [Срок оценки: 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 [Срок оценки: Adverse events will be monitored up to 12 months after completion of chemotherapy, with chemotherapy administered for up to 18 weeks.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Beth Israel Deaconess Medical Center — Boston

Идентификаторы

NCT: NCT07654426 · 25-814

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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