RECRUITING

Effect of Moderate Renal Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics

Conditions

Acute Myeloid Leukaemia (AML)Myelodysplastic Syndrome (MDS)Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)Pharmacokinetic

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study aim is to assess, if treosulfan pharmacokinetics are influenced by declined renal function and by race/ethnicity of patients. The study also aims to determine an appropriate safe dose of treosulfan, when patient's renal function is impaired. The participants of this study are undergoing allogenic hematopoietic stem cell transplantation for treatment of acute myeloid leukemia or myelodysplastic syndrome.

Official Title

An Open-label, Non-randomized, Prospective Trial to Evaluate the Effect of Renal Function Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics in Patients With AML or MDS Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Quick Facts

Study Start:2024-02-01

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05534620

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participants with AML or MDS who qualify for treosulfan-based conditioning treatment, indicated for alloHSCT. 2. Have available matched-related, matched-unrelated, haploidentical, or a mismatched unrelated donor. Match is defined as at least 9/10 allele matches in human leucocyte antigen (HLA)-A, -B, -C, -DRB1 and DQB1 or 7/8 allele matches in (HLA)-A, -B, -C and -DRB1. Haploidentical is defined as any family member with 2, 3 or 4 (out of 8) HLA-loci mismatch; at the same time, the donor and recipient must be HLA identical for at least one antigen at the following genetic loci: (HLA)-A, -B, -C, and -DRB1. High resolution deoxyribonucleic acid (DNA) typing must be used. 3. Are adults of either sex, age 18-80 years (inclusive). 4. Have a Karnofsky Index of greater than or equal to (\>=) 60 percent (%). 5. Have a creatinine clearance (CLcre) \>=30 milliliters per minute (mL/min) (Cockcroft Gault: normal renal function: CLcre \>=90 mL/min, mild renal impairment: CLcre 60-89 mL/min, moderate renal impairment: CLcre 30-59 mL/min). 6. Are willing to consent to using a highly effective method of birth control, such as condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner while on treatment and for at least 6 months thereafter, if females of childbearing potential (defined according to the Clinical Trials Facilitation and Coordination Group guidelines as a fertile woman, following menarche and until becoming postmenopausal unless permanently sterile) and males capable of reproduction. 7. Have a negative pregnancy test, if females of childbearing potential. 8. Have provided a written informed consent.	1. Participants considered not eligible for alloHSCT, for instance due to severe concomitant illness, within 3 weeks before the scheduled Baseline Visit: * Have severe renal impairment, example, are on dialysis, have renal transplantation history, or calculated CLcre of less than (\<) 30 mL/min. * Have severe pulmonary impairment, single-breath diffusion capacity of the lung for carbon monoxide (DLCO) (haemoglobin adjusted) or forced expiratory volume (FEV1) of \<50%, or severe dyspnoea at rest or requiring oxygen supplementation. * Have moderate or severe hepatic impairment (Child-Pugh B or C classification, respectively) and with documented medical history of chronic liver disease.. 2. Have a known coronary artery disease, history of myocardial infarction, cardiac dysfunction, including cardiomyopathies, heart failure (New York Heart Association Class II and above), and cardiac arrhythmias (including paroxysmal and permanent atrial fibrillation), interventricular conduction delay and / or bundle branch block (QRS duration \>120 milliseconds \[ms\]). 3. Have Fredericia-corrected QTc (QTcF) interval \>450 ms in men and \>470 ms in women. 4. Have active malignant involvement of the central nervous system. 5. Are human immunodeficiency virus (HIV) positive or have an active non controlled infectious disease under treatment including fungal infection, active viral liver infection, or known severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) viral infection at the time of enrolment. 6. Have previously had more than one alloHSCT. 7. Have pleural effusion or ascites of \>1.0 liters (L). 8. Are pregnant or breast-feeding. 9. Have uncontrolled or severe intercurrent medical condition. 10. Have known hypersensitivity to treosulfan, fludarabine, and / or related ingredients, Fanconi anaemia and other disorders resulting from DNA repair disorders. 11. Are participating in another experimental drug trial (except those for coronavirus disease \[COVID 19\] vaccines) within 4 weeks prior to the Day 7 Baseline Visit. This exception serves to comply with subject's interests as this population is at a high risk of COVID 19 complications, if the disease occurs. COVID 19 vaccination details (including vaccine name, batch and manufacturer, dose, date of administration, and whether the right or left arm was injected) should be captured as a concomitant medication to enable better assessment of the overall effect of COVID 19 vaccination on oncology trial results. 12. Exhibit non cooperative behaviour or non compliance. 13. Have psychiatric diseases or conditions that might compromise the ability to give informed consent.

Inclusion Criteria

Exclusion Criteria

1. Participants with AML or MDS who qualify for treosulfan-based conditioning treatment, indicated for alloHSCT.
2. Have available matched-related, matched-unrelated, haploidentical, or a mismatched unrelated donor. Match is defined as at least 9/10 allele matches in human leucocyte antigen (HLA)-A, -B, -C, -DRB1 and DQB1 or 7/8 allele matches in (HLA)-A, -B, -C and -DRB1. Haploidentical is defined as any family member with 2, 3 or 4 (out of 8) HLA-loci mismatch; at the same time, the donor and recipient must be HLA identical for at least one antigen at the following genetic loci: (HLA)-A, -B, -C, and -DRB1. High resolution deoxyribonucleic acid (DNA) typing must be used.
3. Are adults of either sex, age 18-80 years (inclusive).
4. Have a Karnofsky Index of greater than or equal to (\>=) 60 percent (%).
5. Have a creatinine clearance (CLcre) \>=30 milliliters per minute (mL/min) (Cockcroft Gault: normal renal function: CLcre \>=90 mL/min, mild renal impairment: CLcre 60-89 mL/min, moderate renal impairment: CLcre 30-59 mL/min).
6. Are willing to consent to using a highly effective method of birth control, such as condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or vasectomised partner while on treatment and for at least 6 months thereafter, if females of childbearing potential (defined according to the Clinical Trials Facilitation and Coordination Group guidelines as a fertile woman, following menarche and until becoming postmenopausal unless permanently sterile) and males capable of reproduction.
7. Have a negative pregnancy test, if females of childbearing potential.
8. Have provided a written informed consent.

1. Participants considered not eligible for alloHSCT, for instance due to severe concomitant illness, within 3 weeks before the scheduled Baseline Visit:
* Have severe renal impairment, example, are on dialysis, have renal transplantation history, or calculated CLcre of less than (\<) 30 mL/min.
* Have severe pulmonary impairment, single-breath diffusion capacity of the lung for carbon monoxide (DLCO) (haemoglobin adjusted) or forced expiratory volume (FEV1) of \<50%, or severe dyspnoea at rest or requiring oxygen supplementation.
* Have moderate or severe hepatic impairment (Child-Pugh B or C classification, respectively) and with documented medical history of chronic liver disease..
2. Have a known coronary artery disease, history of myocardial infarction, cardiac dysfunction, including cardiomyopathies, heart failure (New York Heart Association Class II and above), and cardiac arrhythmias (including paroxysmal and permanent atrial fibrillation), interventricular conduction delay and / or bundle branch block (QRS duration \>120 milliseconds \[ms\]).
3. Have Fredericia-corrected QTc (QTcF) interval \>450 ms in men and \>470 ms in women.
4. Have active malignant involvement of the central nervous system.
5. Are human immunodeficiency virus (HIV) positive or have an active non controlled infectious disease under treatment including fungal infection, active viral liver infection, or known severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) viral infection at the time of enrolment.
6. Have previously had more than one alloHSCT.
7. Have pleural effusion or ascites of \>1.0 liters (L).
8. Are pregnant or breast-feeding.
9. Have uncontrolled or severe intercurrent medical condition.
10. Have known hypersensitivity to treosulfan, fludarabine, and / or related ingredients, Fanconi anaemia and other disorders resulting from DNA repair disorders.
11. Are participating in another experimental drug trial (except those for coronavirus disease \[COVID 19\] vaccines) within 4 weeks prior to the Day 7 Baseline Visit. This exception serves to comply with subject's interests as this population is at a high risk of COVID 19 complications, if the disease occurs. COVID 19 vaccination details (including vaccine name, batch and manufacturer, dose, date of administration, and whether the right or left arm was injected) should be captured as a concomitant medication to enable better assessment of the overall effect of COVID 19 vaccination on oncology trial results.
12. Exhibit non cooperative behaviour or non compliance.
13. Have psychiatric diseases or conditions that might compromise the ability to give informed consent.

Contacts and Locations

Study Contact

Ute Eckenbach

CONTACT

+49 6074 486 2036

ute.eckenbach@synteract.com

Study Locations (Sites)

University of Illinois

Chicago, Illinois, 60612

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10021

United States

The Ohio State University

Columbus, Ohio, 43210

United States

VCU Massey Cancer Center

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: medac GmbH

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-02-01

Study Completion Date2025-12

Study Record Updates

Study Start Date2024-02-01

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

Pharmacokinetic

Additional Relevant MeSH Terms

Acute Myeloid Leukaemia (AML)
Myelodysplastic Syndrome (MDS)
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)