Trial Title:
Effect of Moderate Renal Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics
NCT ID:
NCT05534620
Condition:
Acute Myeloid Leukaemia (AML)
Myelodysplastic Syndrome (MDS)
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Conditions: Official terms:
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Fludarabine
Treosulfan
Conditions: Keywords:
Pharmacokinetic
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Treosulfan
Description:
IV infusion
Arm group label:
Treosulfan and Fludarabine
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
IV infusion
Arm group label:
Treosulfan and Fludarabine
Summary:
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.
Criteria for eligibility:
Criteria:
Inclusion 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.
Exclusion Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Illinois
Address:
City:
Chicago
Zip:
60612
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Chukwuemeka Uzoka
Email:
cuzoka2@uic.edu
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Boglarka Gyurkocza
Email:
gyurkocb@mskcc.org
Facility:
Name:
The Ohio State University
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sarah Wall
Email:
Sarah.Fortier@osumc.edu
Facility:
Name:
VCU Massey Cancer Center
Address:
City:
Richmond
Zip:
23298
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
William Clark
Email:
william.clark@vcuhealth.org
Start date:
February 1, 2024
Completion date:
December 2025
Lead sponsor:
Agency:
medac GmbH
Agency class:
Industry
Collaborator:
Agency:
Synteract, Inc.
Agency class:
Industry
Source:
medac GmbH
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05534620
