Combination Salvage Therapy With Venetoclax and Decitabine in Relapsed/Refractory AML

NCT06156579 | Recruiting Phase 2 DMC

• 1 other identifier: VenSwitch
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this prospective, phase II single center, one arm, open label clinical trial is to test the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in patients with newly diagnosed AML (acute myeloid leukemia) and primary induction failure and patients with relapse of AML/MDS IB2 (myelodysplastic neoplasm with increased blasts 2) after chemotherapy. The primary endpoint is hematologic remission after treatment with Decitabine and Venetoclax. Participants eligible for the trial will receive a treatment of ten days of Decitabine and twenty-eight days of Venetoclax for one or two cycles, after which hematological remission will be assessed. Follow up will include the first one hundred days after end of treatment.

Conditions

AML; MDS

Keywords

Venetoclax; Decitabine; salvage therapy

Outcome Measures

Primary Outcomes (1)

• Rate of hematological remissions

  Hematologic remission (defined as morphologically leukemia-free state (MLFS), complete remission (CR), complete remission with incomplete hematological recovery (CRi) or complete remission with partial hematological recovery (CRh)) as best response in bone marrow aspiration cytomorphology\*) after one or two cycles of Decitabine/Venetoclax. \* or bone marrow pathology, if aspiration morphology not available, not representative or not judged sufficiently reliable by treating physician

  measured after the first and second cycle (each cycle is 28 days)

Secondary Outcomes (11)

• Rate of CTCAEs ≥ Grade 3

  observed during the first and second cycle (each cycle is 28 days) and until day 30 after therapy application

• Time to hematopoietic recovery in days

  after each chemotherapy treatment cycle (28 days), defined as the time from the start of the cycle until recovery

• Rate of MRD-negativity (measurable residual disease)

  measured at each remission assessment (C1D15, C1D28, C2D28, Follow Up)

• Rate of infectious complications CTCAEs ≥ grade 3

  measured during the first and second cycle and the first 30 days after end of treatment (each cycle is 28 days)

• Time to transplant in days

  until day 100 after end of treatment

Study Arms (1)

Treatment

EXPERIMENTAL

Salvage therapy with Venetoclax and intensified Decitabine

Drug: Decitabine; Drug: Venetoclax

Interventions

Decitabine DRUG

Decitabine 20 mg/m\^2, i.v., once daily, 10 days

Also known as: Dacogen

Treatment

Venetoclax DRUG

Venetoclax, 400 mg, p.o., once daily, 28 days

Also known as: Venclyxto, Venclexta

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Diagnosis of AML according to WHO criteria regardless of subtype, including de novo and transformed MPN and transformed MDS 2. A. Refractory to induction chemotherapy consisting of Daunorubicin+Cytarabin ("3+7") based chemotherapy, including CPX351, including combinations with GemtuzumabOzogamicin or with the FLT3-inhibitors Midostaurin or Quizartinib. This trial defines refractory disease as one of the following: i. ≥20% bone marrow blasts\*\* at day 15\*\*\* first cycle of intensive induction chemotherapy ii. ≥5-20% bone marrow blasts\*\* at day 15\*\*\* of first cycle of intensive induction chemotherapy in patients, in whom relative blast count reduction as compared to initial diagnosis is ≤50% iii. c) ≥5% bone marrow blasts\*\* at day 28\*\*\*\* of first cycle of induction chemotherapy, or at any point during a second cycle of induction chemotherapy OR 2. B. Relapse of AML/MDS IB2 after chemotherapy (≥5% medullary blasts in bone marrow assessment\*\*) 3. Must be ≥ 18 years at the time of signing the informed consent. 4. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. 5. Able to adhere to the study visit schedule and other protocol requirements. 6. Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist 7. No known history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide (DLCO) \>40% (adjusted for hemoglobin, if available) and FEV1/FVC \>50% 8. Subject (male or female (FCBP))1 is willing to use highly effective birth control methods during treatment and for 3 months (male) and 6 months (female) after the end of treatment (adequate: combined hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition ofvulation, intrauterine device, intrauterine hormone-releasing system bilateral tubal occlusion, vasectomized partner2 sexual abstinence3). Female subjects who use hormonal contraceptives should also use a barrier method.
• A FCBP is defined as any female who does not meet the criteria of non-childbearing potential. These are as follows:
• documented hysterectomy, bilateral oophorectomy (ovarectomy), or bilateral tubal ligation
• post-menopausal (a practical definition accepts menopause ≥ 1 year without menses with an appropriate clinical profile, e.g. age \> 45 years in the absence of hormone replacement therapy (HRT). In questionable cases, the subject must have a follicle stimulating hormone (FSH) value \> 40 mIU/ml and an estradiol value \< 40pg/ml.
• Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success
• In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 9. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment. 10. All subjects must agree not to share medication.
• in bone marrow aspiration cytomorphology, or bone marrow pathology, if aspiration morphology not available or not representative \*\*\* time frame of tolerance from day 13 to day 20 \*\*\*\*time frame of tolerance from day 21 to day 42

You may not qualify if:

• APL (AML with t (15;17))
• Not consenting to chemotherapy in general
• Previous Treatment with allogeneic stem cell transplantation
• ECOG \>3
• Medical History of hypersensitivity to to the active substances of Venetoclax and Decitabin or to any of the excipients listed in the respective SmPCs
• Relapsed FLT3-ITD- or FLT3-TKD-mutated patients, who previously responded (CR, CRi, CRh or MLFS) to a regimen containing a FLT3-inhibitor.
• Women during pregnancy and lactation.
• Significant active cardiac disease within 6 months prior to the start of study treatment, including:
• New York Heart Association (NYHA) class III or IV congestive heart failure;
• Myocardial infarction;
• Unstable angina and/or stroke;
• Severe cardiac arrhythmias
• Left ventricular ejection fraction (LVEF) \<40% by ultrasound obtained within 28 days prior to the start of study treatment.
• Severe obstructive or restrictive ventilation disorder
• Clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. (Note: Evaluation of cerebrospinal fluid (CSF) during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening)

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

MeSH Terms

Interventions

Decitabine; venetoclax

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Claudia Lengerke, Prof.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucas Mix, Dr.

CONTACT

(+49)70712961781; lucas.mix@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single center, one arm, open label clinical trial

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: December 5, 2023
• Study Start: November 4, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)