Trial Title:
Venetoclax in Addition to Sequential Conditioning With Fludarabine / Amsacrine / Ara-C (FLAMSA) + Treosulfan for Allogeneic Blood Stem Cell Transplantation in Patients With MDS, CMML or sAML
NCT ID:
NCT05807932
Condition:
Myelodysplastic Syndromes
Secondary Acute Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Mycophenolic Acid
Venetoclax
Amsacrine
Tacrolimus
Conditions: Keywords:
MDS
sAML
CMML
allogeneic blood stem cell transplantation
Venetoclax
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Study treatment consists of the conditioning therapy including 6 or 8 days of Venetoclax
treatment.
Arm group label:
Venetoclax
Intervention type:
Drug
Intervention name:
Amsacrine
Description:
Amsacrine is part of the conditioning therapy and is administered on day -10 to -7 before
allogeneic blood stem cell transplantation
Arm group label:
Venetoclax
Intervention type:
Drug
Intervention name:
Ara-C
Description:
Ara-C is part of the conditioning therapy and is administered on day -10 to -7 before
allogeneic blood stem cell transplantation
Arm group label:
Venetoclax
Intervention type:
Drug
Intervention name:
Tacrolimus
Description:
Tacrolimus is used for prophylaxis of acute and chronic graft-versus-host-disease
according to institutional standards.
Arm group label:
Venetoclax
Intervention type:
Drug
Intervention name:
Mycophenolate Mofetil
Description:
Mycophenolate Mofetil is used for prophylaxis of acute and chronic
graft-versus-host-disease according to institutional standards.
Arm group label:
Venetoclax
Summary:
This trial aims to find the MTD of Venetoclax when added to Fludarabin, Amsacrine and
Ara-C + Treosulfan and to evaluate whether the addition of Venetoclax to sequential
conditioning with FLAMSA + Treosulfan is safe for allogeneic blood stem cell
transplantation in patients with high-risk MDS, CMML or sAML (FLAMSAClax)
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subjects must voluntarily sign and date an informed consent, approved by an
independent ethics committee (IEC), prior to the initiation of any study-specific
procedures
- MDS, CMML or sAML according to WHO classification (revised version 2016) with a
marrow blast count >5% and/or high-risk genetic features (e.g. bad risk karyotype
according to the IPSS-R / ELN classification or presence of unfavorable somatic
mutations (e.g. TP53, RUNX1, IDH1, IDH2, KMT2A, DEK-NUP214 or RAS pathway mutations
including NRAS, KRAS, PTPN11, CBL, NF1, RIT1 or KIT), falling into the "high" or
"very high" risk category of the IPSS-R or IPSS-M) any time between diagnosis and
inclusion
- Untreated except for oral Hydroxyurea or a maximum of 2 courses of treatment with
Azacytidine or Decitabine alone or in combination with Venetoclax
- Identification of a well matched (10 out of 10, A, B, C, DR, DQ) donor either
related or unrelated
- Age ≥18
- HCT-CI ≤ 3 (except former treatment of a solid tumor)
- ECOG performance status ≤ 2 at study entry
- no active, uncontrolled infection at inclusion
- able to adhere to the study visit schedule and other protocol requirements
- Female of childbearing potential (FCBP) must:
- Understand that based on embryo-foetal toxicity studies in animals venetoclax
may harm the foetus when administered to pregnant woman
- Agree to have a medically supervised pregnancy test at Screening and within 72
hours prior treatment start
- Avoid becoming pregnant while receiving Venetoclax
- Use effective contraception during treatment with Venetoclax and for at least 1
months after the last dose,
- Understand that is currently unknown whether venetoclax may reduce the
effectiveness of hormonal contraceptives, and therefore women using hormonal
contraceptives should add a barrier method
- Notify her study doctor immediately if there is a risk of pregnancy
- Males must:
- agree to use condoms, even if the male subject has undergone a successful
vasectomy, from Study Day 1 through at least 30 days after the last dose of
study drug.
- Agree to notify the investigator immediately, if pregnancy or a positive
pregnancy test occurs in his partner during study participation
Exclusion Criteria:
- sAML with known FLT3 mutation (ITD or TKD)
- Marrow blast count >30% at the time of screening
- Peripheral white blood count >20,000 per microliter despite treatment with
Hydroxyurea
- previous cytotoxic therapy exceeding oral Hydroxyurea or >2 courses of treatment
with Azacytidine, Decitabine or low dose Ara-C alone or in combination with
Venetoclax
- previous allogeneic blood stem cell transplantation
- symptomatic CNS-involvement with MDS; CMML or sAML
- any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form
- pregnant or lactating females
- Refusal to use safe contraceptive methods during the study period
- Cardiac history of CHF (>NYHA 2) requiring treatment or Ejection Fraction < 40% or
chronic stable angina
- Forced expiratory volume in 1 second (FEV1) <50% of expected corrected for
hemoglobin and/or volume
- Diffusing capacity of the lungs for carbon monoxide (DLCO) <50% of expected
corrected for hemoglobin and/or volume
- any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study:
- Impaired renal function (GFR < 45 ml/min)
- Impaired hepatic function, as follows Aspartate aminotransferase (AST) ≥3 x ULN
or Alanine aminotransferase (ALT) ≥3 x ULN or Total bilirubin ≥1.5 x ULN
(unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
or Alkaline Phosphatase ≥3 x ULN
- known hypersensitivity to Venetoclax, Fludarabine, Amsacrine, Ara-C or Treosulfan
- concurrent use of other anti-cancer agents or treatments except Hydroxyurea and a
maximum of 2 courses of Azacytidine or Decitabine
- positive for HIV or replicating infectious hepatitis, type A, B, C or E
- prior history of malignancy other than MDS, CMML, sAML (except basal cell or
squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the
subject has been free of disease for ≥ 2 years
- participation in another study with ongoing use of unlicensed investigational
product from 28 days or <5 half-lifes of the investigational product before study
enrollment
- No planned or executed/given treatment with any of the following within 7 days prior
to the first dose of study drug (or ramp-up prophase):
- Steroid therapy for anti-neoplastic intent
- moderate or strong cytochrome P450 3A (CYP3A) inhibitors
- moderate or strong CYP3A inducers
- Refusal to avoid consumption of any of the following within 3 days prior to the
first dose of study drug: grapefruit or grapefruit products, Seville oranges
(including marmalade containing Seville oranges), star fruit.
- Persons with any kind of dependency on the investigator or employed by the sponsor
or investigator
- Persons held in an institution by legal or official order
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Universitätsklinikum Aachen - Med. Klinik IV
Address:
City:
Aachen
Zip:
52074
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Edgar Jost, Prof. Dr.
Investigator:
Last name:
Edgar Jost, Prof. Dr.
Email:
Principal Investigator
Facility:
Name:
Universitätsklinikum Düsseldorf - Klinik für Hämatologie, Onkologie und Klinische Immunologie
Address:
City:
Düsseldorf
Zip:
40225
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Guido Kobbe, Prof. Dr.
Email:
kobbe@med.uni-duesseldorf.de
Investigator:
Last name:
Guido Kobbe, Prof. Dr.
Email:
Principal Investigator
Facility:
Name:
Universitätsklinikum Frankfurt Medizinische Klinik II
Address:
City:
Frankfurt
Zip:
60590
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Gesine Bug, PD Dr.
Facility:
Name:
Universitätsklinikum Jena - Klinik für Innere Medizin II
Address:
City:
Jena
Zip:
07747
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Inken Hilgendorf, Prof. Dr.
Investigator:
Last name:
Inken Hilgendorf, Prof. Dr.
Email:
Principal Investigator
Facility:
Name:
Universitätsklinikum Köln Klinik I für Innere Medizin
Address:
City:
Köln
Zip:
50937
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Udo Holtick, PD Dr.
Facility:
Name:
Klinikum rechts der Isar der TU München Klinik und Poliklinik für Innere Medizin III
Address:
City:
München
Zip:
81675
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Mareike Verbeek, Dr.
Start date:
June 26, 2023
Completion date:
January 30, 2028
Lead sponsor:
Agency:
Heinrich-Heine University, Duesseldorf
Agency class:
Other
Collaborator:
Agency:
Koordinierungszentrum für Klinische Studien - Duesseldorf
Agency class:
Other
Source:
Heinrich-Heine University, Duesseldorf
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05807932
