ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03589729
Recruitment Status : Recruiting
First Posted : July 18, 2018
Last Update Posted : November 8, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Blasts 10 Percent or More of Bone Marrow Nucleated Cells High Risk Myelodysplastic Syndrome Myeloid Sarcoma Myeloproliferative Neoplasm Philadelphia Chromosome Positive Drug: Cladribine Drug: Cytarabine Drug: Dexrazoxane Hydrochloride Drug: Gemtuzumab Ozogamicin Drug: Idarubicin Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
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
Actual Study Start Date : September 19, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Supportive care (dexrazoxane hydrochloride, chemotherapy)
See detailed description.
Drug: Cladribine
Given IV
Other Names:
  • 2-CdA
  • 2CDA
  • CdA
  • Cladribina
  • Leustat
  • Leustatin
  • Leustatine
  • RWJ-26251

Drug: Cytarabine
Given IV
Other Names:
  • .beta.-Cytosine arabinoside
  • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-.beta.-D-Arabinofuranosylcytosine
  • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
  • 1-Beta-D-arabinofuranosylcytosine
  • 1.beta.-D-Arabinofuranosylcytosine
  • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
  • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
  • Alexan
  • Ara-C
  • ARA-cell
  • Arabine
  • Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Aracytidine
  • Aracytin
  • Aracytine
  • Beta-cytosine Arabinoside
  • CHX-3311
  • Cytarabinum
  • Cytarbel
  • Cytosar
  • Cytosine Arabinoside
  • Cytosine-.beta.-arabinoside
  • Cytosine-beta-arabinoside
  • Erpalfa
  • Starasid
  • Tarabine PFS
  • U 19920
  • U-19920
  • Udicil
  • WR-28453

Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Totect
  • Zinecard

Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
  • Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
  • CDP-771
  • CMA-676
  • gemtuzumab
  • hP67.6-Calicheamicin
  • Mylotarg
  • WAY-CMA-676

Drug: Idarubicin
Given IV
Other Names:
  • 4-Demethoxydaunomycin
  • 4-demethoxydaunorubicin
  • 4-DMDR




Primary Outcome Measures :
  1. Percentage of patients experiencing a decrease in left ventricular ejection fraction (LVEF) [ Time Frame: Baseline up to 6 months ]
    Will assess a decrease in LVEF of 10 percent from baseline or decrease in LVEF below the normal limit of 50% during treatment with dexrazoxane hydrochloride combined with cladribine, idarubicin, cytarabine, and gemtuzumab ozogamicin.


Secondary Outcome Measures :
  1. Incidence of cardiac symptoms [ Time Frame: Up to 1 year ]
    Cardiac symptoms to be evaluated include: clinical heart failure, exertional dyspnea, orthopnea, S3 gallop, acute coronary syndrome, acute pulmonary edema and life-threatening arrhythmias

  2. Assessment of change in troponin I and high-sensitivity troponin T [ Time Frame: Up to 1 year ]
    Troponin levels will be collected before and after the day 1 dose of idarubicin each month during induction, consolidation, and maintenance therapy.

  3. Incidence of adverse events [ Time Frame: Up to 1 year ]
  4. Complete remission (CR) /complete remission with incomplete blood count recovery (CRi) rates (Cohorts 1-3) [ Time Frame: Up to 1 year ]
  5. Overall response (Cohorts 1-3) [ Time Frame: Up to 1 year ]
  6. Overall survival (Cohorts 1-3) [ Time Frame: Up to 1 year ]
  7. Event-free survival (Cohorts 1-3) [ Time Frame: Up to 1 year ]
  8. Remission duration (Cohorts 1-3) [ Time Frame: Up to 1 year ]
  9. Recurrence-free survival [ Time Frame: Up to 6 months ]
    The recurrence-free survival rate at 6 months will be a binary endpoint where the recurrence including death occurred within 6 months of treatment will be considered as "recurrence event".


Other Outcome Measures:
  1. Assessment of metal chelation effects of dexrazoxane and chemotherapy [ Time Frame: Up to 1 year ]
    Metal chelation effects assessed by utilizing technologies commonly used in the geochemistry.

  2. Assessment of minimal residual disease (MRD) [ Time Frame: Up to 1 year ]
    Will explore the impact of MRD on relapse.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Baseline left ventricular ejection fraction (LVEF) is greater than or equal to 50% by echocardiography (echo) or multigated acquisition (MUGA) scan.
  • Patients of child bearing potential should use contraception.
  • Patients with a diagnosis of acute myeloid leukemia (AML), or high risk myelodysplastic syndrome (MDS) (>= 10% blasts or International Prognostic Scoring System [IPSS] >= intermediate-2) or high-risk myeloproliferative neoplasm will be eligible.
  • Patients with untreated or previously untreated chronic myeloid leukemia (CML) in myeloid blast phase or (Philadelphia chromosome-positive (Ph+) AML are also eligible.
  • Patients with myeloproliferative neoplasms in blast phase will be eligible.
  • Patients with isolated extramedullary myeloid neoplasm will be eligible.
  • Patients with active CNS (central nervous system) disease are eligible.
  • Bilirubin < 2mg/dL.
  • AST (aspartate aminotransferase) and/or ALT (alanine aminotransferase) < 3 x ULN (upper limit of normal) - or < 5 x ULN if related to leukemic involvement.
  • Creatinine < 1.5 x ULN.
  • Hyperbilirubinemia is allowed if due to Gilbert's hyperbilirubinemia.
  • A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
  • Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
  • Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.
  • Prior therapy for any of the cohorts may include with hydroxyurea, rescue doses of cytarabine, various combination-chemotherapy regimens, hematopoietic growth factors, azacytidine, decitabine, ATRA (all-trans retinoic acid).
  • Cohort 1: Frontline cohort patients are eligible in the frontline cohort if they are untreated or previously treated already in CR if they received 3 or fewer cycles of previous chemotherapy (including either 1 induction and 2 consolidations or 2 inductions and 1 consolidation).
  • Cohort 2: Salvage cohort in 1st and 2nd salvage patients are eligible in the salvage cohort 2 if they have active disease after first or second relapse or if they are in CR after previously documented first or second relapse as long as they if they have received 3 or fewer cycles of chemotherapy to achieve the most current CR.
  • Cohort 3: Salvage cohort in 3rd salvage and beyond patients may be eligible in salvage cohort 3 if they have active disease after 3rd or greater relapse or if they are in CR after a previously documented relapse (3rd or greater), but may have only received 3 or fewer cycles of chemotherapy to achieve the most current CR.
  • Cohort 4: Maintenance cohort: Patients in CR who are considered by treating physician to benefit from maintenance therapy are eligible for maintenance therapy with dexrazoxane combined with idarubicin plus cytarabine.

Exclusion Criteria:

  • Any condition, including the presence of laboratory abnormalities, which judged by the investigator, places the patient at unacceptable risk.
  • Active heart disease defined as: Unstable coronary syndromes, unstable or severe angina, recent myocardial infarction (MI) within 6 months.
  • Decompensated heart failure (HF).
  • Clinically significant arrhythmias.
  • Severe valvular disease.
  • History of coronary artery disease (CAD).
  • Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
  • Psychiatric illness/social situations that would limit compliance with study requirements per the judgment of the investigator.
  • Patient with documented hypersensitivity to any of the components of the chemotherapy program.
  • Men and women of childbearing potential who do not practice contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03589729


Contacts
Contact: Maro Ohanian 713-792-2631 mohanian@mdanderson.org

Locations
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Maro Ohanian    713-792-2631      
Principal Investigator: Maro Ohanian         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Maro Ohanian M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03589729     History of Changes
Other Study ID Numbers: 2017-0937
NCI-2018-01108 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0937 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 18, 2018    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Sarcoma, Myeloid
Sarcoma
Syndrome
Leukemia
Neoplasms
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myeloproliferative Disorders
Philadelphia Chromosome
Blast Crisis
Disease
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Translocation, Genetic
Chromosome Aberrations
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Neoplasms, Connective and Soft Tissue
Cytarabine
Cladribine
Gemtuzumab
Idarubicin
Dexrazoxane