Dexrazoxane Hydrochloride in Preventing Heart-Related Side Effects of Chemotherapy in Participants With Blood Cancers

Acute Myeloid Leukemia Clinical Trial

Official title: Cardioprotection With Dexrazoxane in Acute Myeloid Leukemia (AML), High-Risk Myelodysplastic Syndrome (MDS), Myeloid Blast Phase of Chronic Myeloid Leukemia (CML), Ph+ AML, and Myeloid Blast Phase of Myeloproliferative Neoplasms

Status Recruiting

Clinical Trial Summary

This phase II trial studies how well dexrazoxane hydrochloride works in preventing heart-related side effects of chemotherapy in participants with blood cancers, such as acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, and myeloproliferative neoplasms. Chemoprotective drugs, such as dexrazoxane hydrochloride, may protect the heart from the side effects of drugs used in chemotherapy, such as cladribine, idarubicin, cytarabine, and gemtuzumab ozogamicin, in participants with blood cancers.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To estimate the percentage of patients experiencing a decrease in left ventricular ejection fraction (LVEF) of 10 percent from baseline or decrease in LVEF below the normal limit of 50% during treatment with dexrazoxane (dexrazoxane hydrochloride) combined with cladribine, idarubicin, cytarabine, and Mylotarg (gemtuzumab ozogamicin) within the first 6-months of treatment.

SECONDARY OBJECTIVES:

I. To estimate the incidence of these cardiac symptoms while on dexrazoxane combined with idarubicin-based treatment: clinical heart failure, exertional dyspnea, orthopnea, S3 gallop, acute coronary syndrome, acute pulmonary edema and life-threatening arrhythmias.

II. To assess and monitor the change of troponin I (while still standard of care at MD Anderson) and high-sensitivity troponin T during treatment.

III. Collect safety/toxicity profile. IV. To assess rates of complete remission (CR)/complete remission with incomplete blood count recovery (CRi). (Cohorts 1-3) V. Other efficacy endpoints of interest include overall response, overall survival, event-free survival and remission duration. (Cohorts 1-3) VI. To assess the recurrence-free survival rate at 6 months. (Cohort 4)

EXPLORATORY OBJECTIVES:

I. To assess the metal chelation effects of dexrazoxane combined with chemotherapy (Mylotarg, cladribine, idarubicin, and cytarabine) by quantifying concentrations of toxic and essential metals and isotopic abundance ratios of blood and bone marrow before and during treatment.

II. To study and describe the relationship between pretreatment patient / disease characteristics (including cytogenetic and molecular abnormalities) and clinical outcomes.

III. To identify molecular biomarkers predictive of response to therapy. IV. To study and describe the relationship between patient / disease characteristics, use of intrathecal prophylaxis, and incidence of leptomeningeal disease.

V. To observe rates of fungal and other infections on the regimen. VI. To study environmental exposure data based on an environmental health assessment survey.

VII. To explore the impact of minimal residual disease (MRD) on relapse.

OUTLINE:

INDUCTION PHASE: Participants receive gemtuzumab ozogamicin intravenously (IV) over 2 hours on days 1, 4, and 7, cladribine IV over 1-2 hours on days 1-5, dexrazoxane hydrochloride IV over 15 minutes on days 1-3, idarubicin IV over 30 minutes on days 1-3, and cytarabine IV over 2 hours on days 1-5. Treatment repeats every 3-7 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION PHASE: After induction phase, participants receive gemtuzumab ozogamicin IV over 2 hours on day 1, cladribine IV over 1-2 hours on days 1-3, dexrazoxane hydrochloride IV over 15 minutes on days 1-2, idarubicin IV over 30 minutes on days 1-2, and cytarabine IV over 2 hours on days 1-3. Treatment repeats every 3-7 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Participants who go into remission or who are already in remission receive gemtuzumab ozogamicin IV over 2 hours on day 1 of course 1 and then every 2-3 months as needed. Participants also receive dexrazoxane hydrochloride IV over 15 minutes and idarubicin IV over 30 minutes on day 1, and cytarabine subcutaneously (SC) on days 1-7. Courses repeat every 3-7 weeks for 32 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 6-12 months. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Blast Crisis
• Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Blasts 10 Percent or More of Bone Marrow Nucleated Cells
• High Risk Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myeloid Sarcoma
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Philadelphia Chromosome
• Philadelphia Chromosome Positive
• Preleukemia
• Sarcoma, Myeloid

• NCT number: NCT03589729
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Maro Ohanian
• Phone: 713-792-2631
• Email: mohanian@mdanderson.org
• Status: Recruiting
• Phase: Phase 2
• Start date: September 19, 2018
• Completion date: December 31, 2025