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Purpose

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

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 1. LVEF 30-50% on most recent echocardiogram with or without HF history 2. LVEF 50% with a history of HF (i.e. HF with improved EF or HF with preserved EF). 3. 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Double Blind

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
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: - Baseline visit - Cycle 1 through End of Treatment (21 day cycles): - Day 1: predetermined dose of Dexrazoxane 1x daily - Day 1: predetermined dose of Doxorubicin 1x daily - Standard of care R-CHOP per protocol - 3 and 12 month follow up post-standard of care treatment completion - Long term follow up: annually from year 2 - 5
  • Drug: Dexrazoxane
    Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • C11H16N4O4
  • Drug: Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, C27H29NO11•HCL, ADRIAMYCIN, FI-106
  • Drug: Cyclophosphamide
    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
    Other names:
    • C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE
  • Drug: Vincristine
    vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
    Other names:
    • Vincristine Sulfate, C46H56N4O10
  • Drug: Prednisone
    Glucocorticoid, tablet taken orally per standard of care.
    Other names:
    • C21H26O5
  • Drug: Rituximab
    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
    Other names:
    • Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586
Placebo Comparator
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: - Baseline visit - Cycle 1 through End of Treatment (21 day cycles): - Day 1: predetermined dose of Dexrazoxane placebo 1x daily - Day 1: predetermined dose of Liposomal Doxorubicin 1x daily - Standard of care R-CHOP per protocol - 3 and 12 month follow up post-standard of care treatment completion - Long term follow up: annually from year 2 - 5
  • Drug: Dexrazoxane placebo
    Dexrazoxane placebo via intravenous infusion per protocol.
  • Drug: Liposomal Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, Caelyx, Doxil, TLC-DOXO, PLD, Pegylated Liposomal Doxorubicin, TLC D-99, ATI-0918
  • Drug: Cyclophosphamide
    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
    Other names:
    • C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE
  • Drug: Vincristine
    vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
    Other names:
    • Vincristine Sulfate, C46H56N4O10
  • Drug: Prednisone
    Glucocorticoid, tablet taken orally per standard of care.
    Other names:
    • C21H26O5
  • Drug: Rituximab
    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
    Other names:
    • Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586
Experimental
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 - Cycle 1 through End of Treatment (21 day cycles): - Day 1: predetermined dose of Dexrazoxane 1x daily - Day 1: predetermined dose of Doxorubicin 1x daily - Standard of care pola-R-CHP per protocol - 3 and 12 month follow up post-standard of care treatment completion - Long term follow up: annually from year 2 - 5
  • Drug: Dexrazoxane
    Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • C11H16N4O4
  • Drug: Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, C27H29NO11•HCL, ADRIAMYCIN, FI-106
  • Drug: Cyclophosphamide
    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
    Other names:
    • C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE
  • Drug: Prednisone
    Glucocorticoid, tablet taken orally per standard of care.
    Other names:
    • C21H26O5
  • Drug: Rituximab
    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
    Other names:
    • Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586
  • Drug: Polatuzumab Vedotin
    CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
    Other names:
    • Polatuzumab Vedotin-piiq
Placebo Comparator
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: - Baseline visit - Cycle 1 through End of Treatment (21 day cycles): - Day 1: predetermined dose of Dexrazoxane placebo 1x daily - Day 1: predetermined dose of Liposomal Doxorubicin 1x daily - Standard of care pola-R-CHP per protocol - 3 and 12 month follow up post-standard of care treatment completion - Long term follow up: annually from year 2 - 5
  • Drug: Dexrazoxane placebo
    Dexrazoxane placebo via intravenous infusion per protocol.
  • Drug: Liposomal Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, Caelyx, Doxil, TLC-DOXO, PLD, Pegylated Liposomal Doxorubicin, TLC D-99, ATI-0918
  • Drug: Cyclophosphamide
    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
    Other names:
    • C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE
  • Drug: Prednisone
    Glucocorticoid, tablet taken orally per standard of care.
    Other names:
    • C21H26O5
  • Drug: Rituximab
    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
    Other names:
    • Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586
  • Drug: Polatuzumab Vedotin
    CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
    Other names:
    • Polatuzumab Vedotin-piiq
Other
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: - Baseline visit with assessments and questionnaires - Cycle 1 through End of Treatment (21 day cycles): - Day 1: assessments and questionnaires - Standard of care R-CHOP - 3 and 12 month follow up post-treatment completion - Long term follow up: annually from year 2 - 5, in-person or virtually
  • Drug: Dexrazoxane
    Topoisomerase II Inhibitor, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • C11H16N4O4
  • Drug: Dexrazoxane placebo
    Dexrazoxane placebo via intravenous infusion per protocol.
  • Drug: Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, C27H29NO11•HCL, ADRIAMYCIN, FI-106
  • Drug: Liposomal Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, Caelyx, Doxil, TLC-DOXO, PLD, Pegylated Liposomal Doxorubicin, TLC D-99, ATI-0918
  • Drug: Cyclophosphamide
    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
    Other names:
    • C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE
  • Drug: Vincristine
    vinca alkaloid, single-dose vial, via intravenous infusion per standard of care.
    Other names:
    • Vincristine Sulfate, C46H56N4O10
  • Drug: Prednisone
    Glucocorticoid, tablet taken orally per standard of care.
    Other names:
    • C21H26O5
  • Drug: Rituximab
    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
    Other names:
    • Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586
Other
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: - Baseline visit with assessments and questionnaires - Cycle 1 through End of Treatment (21 day cycles): - Day 1: assessments and questionnaires - Standard of care pola-R-CHP - 3 and 12 month follow up post-treatment completion - Long term follow up: annually from year 2 - 5, in-person or virtually
  • Drug: Dexrazoxane placebo
    Dexrazoxane placebo via intravenous infusion per protocol.
  • Drug: Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, C27H29NO11•HCL, ADRIAMYCIN, FI-106
  • Drug: Liposomal Doxorubicin
    Topoisomerase II Inhibitors, single-dose vial, via intravenous infusion per protocol.
    Other names:
    • doxorubicin hydrochloride, Caelyx, Doxil, TLC-DOXO, PLD, Pegylated Liposomal Doxorubicin, TLC D-99, ATI-0918
  • Drug: Cyclophosphamide
    Lymphodepleting chemotherapy, multi-dose vial, via intravenous infusion per standard of care.
    Other names:
    • C7H15Cl2N2O2P•H2O, Cytoxan, Cyclophosphamide-OE
  • Drug: Prednisone
    Glucocorticoid, tablet taken orally per standard of care.
    Other names:
    • C21H26O5
  • Drug: Rituximab
    Anti-CD20 antibody, single-use vials, via intravenous infusion per standard of care.
    Other names:
    • Riabni, Rituxan, Ruxience, Truxima, ABP 798, IDEC-C2B8, PF-05280586
  • Drug: Polatuzumab Vedotin
    CD79b-directed antibody-drug conjugate, single-dose vial, via intravenous infusion per standard of care.
    Other names:
    • Polatuzumab Vedotin-piiq

Recruiting Locations

Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
Contact:
Jenica Upshaw, MD, MSc
(617) 667-8800
jupshaw@bidmc.harvard.edu

More Details

Status
Recruiting
Sponsor
Beth Israel Deaconess Medical Center

Study Contact

Jenica Upshaw, MD, MSc
(617) 667-8800
jupshaw@bidmc.harvard.edu

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.