A study with three treatments for higher-risk chronic myelomonocytic leukaemia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GCP-Service International West GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

13 May 2025 → ongoing

Decision date (initial)

2025-03-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Stemline Therapeutics, Inc. · AbbVie Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Main objective is the primary objective of the trial is to generate data on the efficacy by CR, mCR, or PR of the combination of the SOC agent AZA combined with venetoclax (VEN) and tagraxofusp (TAG) in the studied patient population in a descriptive manner and by statistical analysis.

Secondary objectives 5

1. Tolerability and safety of the combination
2. Evaluate the efficacy in terms of Overall survival (OS), time to leukemia transformation (TLT), median duration of response until EOT
3. Evaluate the efficacy in terms of Hematologic improvement after 3 cycles of treatment (IWG 2018/2023 criteria)
4. Evaluate the efficacy in terms of Transfusion independence after 3 cycles of treatment (IWG 2018/2023 criteria)
5. Quality of life

Conditions and MedDRA coding

chronic myelomonocytic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Signed written informed consent
2. 2. Male and female ≥ 18 years at date of signing informed consent
3. 3. Must be able to adhere to the study visit schedule and other protocol requirements
4. 4. CMML diagnosis according to WHO 2022 criteria
5. 5. CPSS risk intermediate-2 or high2 (HR) CMML at study entry (WBC prior to HY used to compute CPSS at inclusion in HY-exposed patients, see below)
6. 6. Patients who are eligible for and will receive azacitidine (AZA) as per standard of care.
7. 7. Performance status 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale
8. 8. Adequate organ function including the following: • Liver: o Total bilirubin < 1.5 times upper limit of normal (ULN) (except moderate unconjugated hyperbilirubinemia due to intra medullary hemolysis or due to Gilbert syndrome), AND o Alanine transaminase (ALT) and aspartate transaminase (AST) < 2.5 times ULN • Renal: Creatinine clearance >/= 45 mL/minute • Cardiac o Left ventricular ejection fraction (LVEF) ≥ 50% by multigated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to the start of therapy o No clinically significant abnormalities on a 12-lead electrocardiogram (ECG) • Albumin: Serum albumin ≥ 3.2 g/dL (note: albumin infusions are not permitted in order to enable eligibility)
9. 9. Availability of blood counts and transfusion events for previous 8 weeks
10. 10. Women of childbearing potential and practicing a highly effective method of birth control according to the Clinical Trial Facilitation Coordination Group Recommendation (Version 1.1, 2020)3: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable • intrauterine device (IUD) • intrauterine hormone-releasing system (IUS) • bilateral tubal occlusion • vasectomised partner • sexual abstinence For females, these requirements apply during the treatment period and for 6 months after the end of dosing.
11. 11. A woman of childbearing potential must have a negative serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test within one week of treatment initiation and agree to be tested (serum or urine) on day 1 of every cycle and at EOT
12. 12. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a highly effective method of contraception) and all men must also not donate sperm. Highly effective methods of contraception include double-barrier contraception, total abstinence, vasectomization with confirmed azoospermia, female partner with an intrauterine device, etc.). For males, these requirements apply during the study treatment period and for 3 months after the end of dosing.

Exclusion criteria 25

1. 1. CMML with t (5 ;12) or PDGFRB rearrangement that may be treated with imatinib
2. 2. Myeloproliferative / myelodysplastic neoplasm other than CMML
3. 3. Bone marrow or peripheral blood blasts (including promonocytes) ≥ 20%
4. 4. Patients with unavailable CPSS at inclusion (WBC prior to HY used to compute CPSS at inclusion in HY-exposed patients) or with a CPSS low or intermediate-1 at study entry
5. 5. Patient has received an experimental or investigational drug or used an invasive investigational medical device within 14 days prior to day 1 of C1
6. 6. Prior treatment with TAG, VEN and/or HMA treatment, including AZA/CC-486, decitabine (DEC), SGI-110, AST7227. Prior treatment with Erythropoiesis Stimulating Agents (ESA) or hydroxyurea (HY) is acceptable, with a > 15 days washout from ESAs and > 3 days washout from HY
7. 7. Patients who previously received an allogeneic stem cell transplantation (HSCT) for CMML or an antecedent hematological malignancy. Those never transplanted but eligible for HSCT are eligible for the trial.
8. 8. Major surgery within 4 weeks prior to day 1 of C1 (excluding the placement of vascular access and other minor surgical procedures)
9. 9. Prior malignancy (except in situ cervix carcinoma, limited basal cell carcinoma, asymptomatic prostatic cancer not requiring treatment, or other tumors if not active during the last 2 years)
10. 10. Serious concomitant systemic disorder, including active bacterial, fungal, psychiatric illness, or viral infection that in the opinion of the investigator, would compromise the safety of the patient and/or his/her ability to complete the study.
11. 11. Medical condition requiring therapies with CYP3A inducing activity. All CYP3A inducers should be discontinued 7 days prior to the first dose of study drug
12. 12. Patients with known CNS involvement
13. 13. Females who are pregnant or are currently breastfeeding or planning to become pregnant while enrolled in this study or within 6 months after the end of dosing
14. 14. Patient is a man who plans to father a child while enrolled in this study or within 3 months after the end of dosing
15. 15. The patient is receiving immunosuppressive therapy for any reason, with the exception of low-dose prednisone (≤ 10 mg/day) or equivalent
16. 16. The patient has persistent clinically significant toxicities Grade ≥ 2 from previous therapies, including cytotoxic chemotherapy, targeted therapies, biological therapies, or immunotherapies, not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue)
17. 17. The patient has clinically significant cardiovascular disease (e.g. uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
18. 18. The patient has uncontrolled, clinically significant pulmonary disease (e.g. chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study.
19. 19. The patient has known positive status for human immunodeficiency virus (HIV) or active or chronic Hepatitis B or Hepatitis C.
20. 20. Patient is unable to attend site visits as patient is in custody by order of an authority or a court of law
21. 21. Participation in another interventional clinical study within the last 3 months prior to signing the ICF or simultaneous participation in other clinical studies
22. 22. Previous assignment to treatment during this study
23. 23. Close affiliation with the investigator (e.g. a close relative) or persons working at the study site
24. 24. Patient is an employee of the sponsor or involved CRO
25. 25. Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the patient’s safety

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary outcome measure is the response rate defined as CR or mCR or PR after 3 cycles of treatment.
2. Response will be assessed according to Savona et al., 20151.

Secondary endpoints 5

1. Adverse events (AEs) and serious adverse events (SAEs), clinical laboratory values, vital signs, ECG, and ECHO/MUGA parameters
2. Overall survival (OS), time to leukemia transformation (TLT), median duration of response until EOT
3. Proportion of patients achieving hematologic improvement after 3 cycles of treatment (IWG 2018/2023 criteria)
4. Proportion of patients achieving transfusion independence after 3 cycles of treatment (IWG 2018/2023 criteria)
5. Change of quality of life after 3 cycles and 12 cycles of treatment compared to baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GCP-Service International West GmbH

Sponsor organisation

GCP-Service International West GmbH

Address

Siegfeldstrasse 11

City

Siegburg

Postcode

53721

Country

Germany

Scientific contact point

Organisation

GCP-Service International West GmbH

Contact name

sponsor representativ

Public contact point

Organisation

GCP-Service International West GmbH

Contact name

sponsor representativ

Third parties 8

Locations

3 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications