Phase II Evaluation of Venetoclax and Decitabine in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia Eligible for Allogeneic Stem Cell Transplantation
- Trial ID
- 2024-518792-54-00
- Protocol
- VEN-DEC GITMO
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase II study is to evaluate the proportion of elderly patients aged 60 to 74 years with newly diagnosed **Acute Myeloid Leukemia (AML)** who are eligible for allogeneic Stem Cell Transplantation (allo-SCT) and are treated with the "chemo-free" combination of Venetoclax plus Decitabine (VEN-DEC), achieving complete remission (CR), complete remission with incomplete blood count recovery (CRi), or morphologic leukemia-free state (MLFS) prior to allo-SCT. This is clinically relevant as achieving these remission states is crucial for improving the outcomes of allo-SCT in this patient population.
Secondary objectives include: - Assessing the incidence and severity of adverse drug reactions (ADR) classified by System Organ Class (SOC) and preferred term (PT) from the start of treatment with VEN-DEC to allo-SCT. - Evaluating the efficacy of the VEN-DEC combination. - Evaluating the outcome of allo-SCT in terms of: 1) Incidence of graft failure at day +30 and +100 from allo-SCT. 2) Incidence of Non-Relapse Mortality (NRM) at day +100, 1 year, and 2 years from allo-SCT. 3) Incidence and severity of acute graft-versus-host disease (GVHD) at day +100 from allo-SCT. 4) Incidence and severity of chronic GVHD at 1 year and 2 years from allo-SCT. 5) Probability of GVHD-free, relapse-free survival (GRFS) at 1 and 2 years from allo-SCT. - Relapse incidence (RI) at 1 year and 2 years from allo-SCT. - Disease-free survival (DFS) at 1 and 2 years from allo-SCT. - Overall survival (OS) at 1 and 2 years from allo-SCT. - Correlation of immunophenotype, cytogenetic, molecular, and next-generation sequencing (NGS) genomic profiles with sensitivity (CR/CRi/MLFS) or resistance (partial response [PR]/no response [NR]) to the VEN-DEC combination. - Correlation of immunophenotype, cytogenetic, molecular, and NGS-genomic profiles with the outcome of allo-SCT in terms of NRM, probability of RI, DFS, and OS.
Participants
The clinical trial focuses on evaluating a **chemo-free** treatment combination for patients with **Acute Myeloid Leukemia (AML)**. The study population comprises elderly patients aged between 60 and 74 years, both male and female, who have been newly diagnosed with AML and are eligible for allogeneic stem cell transplantation (allo-SCT). The trial does not include vulnerable populations. Participants are required to have adequate hepatic and renal function, as well as an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or less. The trial population was selected based on specific inclusion criteria, including high- and intermediate-risk European LeukemiaNet (ELN) classification and a white blood cell count of less than 25x10^9/L, with hydroxyurea permitted to meet this criterion. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the trial data.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of a **chemo-free** combination therapy using **venetoclax** and **decitabine** in elderly patients with newly diagnosed **Acute Myeloid Leukemia (AML)** who are eligible for allogeneic stem cell transplantation (allo-SCT). This is a Phase II, randomized, double-blind, controlled trial with an estimated duration from June 29, 2021, to June 25, 2025. The trial aims to assess the proportion of patients achieving complete remission (CR), complete remission with incomplete blood count recovery (CRi), or morphologic leukemia-free state (MLFS) before undergoing allo-SCT.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥60 to <75 years), diagnosis of AML, and adequate organ function. Following the screening, participants will be randomized to receive the investigational treatment. The treatment phase will include regular follow-up visits to monitor efficacy and safety outcomes, with assessments for graft failure, graft-versus-host disease (GvHD), and overall survival (OS) at specified intervals post-transplantation. The end-of-study visit will occur after the final assessment of the primary and secondary endpoints, including disease-free survival (DFS) and relapse incidence (RI).
The expected length of participant involvement is up to 56 days for the treatment period, with additional follow-up extending to 2 years post-transplantation. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is categorized as low-intervention due to the well-tolerated nature of the treatment regimen, which aims to reduce disease burden without increasing toxicity, thereby facilitating the feasibility of allo-SCT as a curative option for this patient population.
Treatment
The clinical trial involves the administration of **Venclyxto** (venetoclax) as part of the treatment regimen. Venclyxto is provided in the form of 100 mg **film-coated tablets**. The active substance, venetoclax, is of chemical origin and is classified under the ATC code L01XX52. The tablets are administered orally, with a maximum daily dose of 400 mg. The treatment period with Venclyxto is limited to a maximum of 5 days. The product is manufactured by AbbVie Deutschland GmbH & Co. KG and has undergone repackaging and re-labeling for the trial. Participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen.
In addition to Venclyxto, the trial includes the administration of **Dacogen** (decitabine). Dacogen is supplied as a 50 mg **powder for concentrate for solution for infusion**. The active substance, decitabine, is also of chemical origin and is classified under the ATC code L01BC08. The solution is administered intravenously, with a maximum daily dose of 20 mg/m². The treatment period with Dacogen extends up to 56 days. This product is manufactured by Janssen-Cilag International NV and has been subject to labeling and packaging modifications for the study. As with Venclyxto, participant compliance with the dosing schedule is closely monitored to ensure proper administration.
Both Venclyxto and Dacogen are utilized as part of a "chemo-free" combination therapy for elderly patients with newly diagnosed **Acute Myeloid Leukemia** (AML) who are eligible for allogeneic stem cell transplantation. The trial aims to evaluate the efficacy of this combination in achieving complete remission, complete remission with incomplete blood count recovery, or morphologic leukemia-free state prior to transplantation.
Efficacy
The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the proportion of elderly patients aged 60 to less than 75 years with newly diagnosed **Acute Myeloid Leukemia (AML)**, eligible for allogeneic Stem Cell Transplantation (allo-SCT), who achieve complete remission (CR), complete remission with incomplete blood count recovery (CRi), or morphologic leukemia-free state (MLFS) after treatment with the "chemo-free" combination of Venetoclax plus Decitabine (VEN-DEC).
Secondary endpoints include the efficacy of the VEN-DEC combination, cumulative incidence of graft failure at 30 and 100 days post-transplant, and outcomes of allo-SCT in terms of non-relapse mortality (NRM) at 100 days, 1 year, and 2 years post-transplant. Additionally, the cumulative incidence and severity of acute graft-versus-host disease (GvHD) at 100 days, and chronic GvHD at 1 and 2 years post-transplant will be evaluated. Relapse incidence (RI) and overall survival (OS) at 1 and 2 years post-transplant, as well as disease-free survival (DFS) at 1 and 2 years post-transplant, will also be assessed.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patients ≥ 60 <75 years of age • Diagnosis of AML eligible for allo-SCT from any donor • High- and Intermediate-Risk ELN • WBC <25x109/L (Hydroxyurea is permitted to meet this criterion) • Adequate hepatic function (bilirubin ≤2 UNL; ALT/AST ≤2,5 UNL) • Adequate renal function (creatinine clearance ≥50 ml/min) • ECOG Performance Status ≤ 2 • Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial. • Women of childbearing potential must use highly effective contraception for at least 1 month after the last dose of VEN and for however long the EU SmPC says for DEC • Willing and able to comply with all of the requirements and visits in the protocol. • Written and signed informed consent.
Exclusion Criteria
- Previous treatment for AML (Hydroxyurea is allowed) or for an antecedent Myelodysplastic Syndrome (MDS) • Subject has known active CNS involvement with AML • Absence of informed consent • AML patients with t(15;17); t(8;21); inv(16) • Low Risk ELN grade > 2 NCI-CTCAE (v. 5) adverse events at the time of enrollment • Serious organ dysfunction: left ventricular ejection fraction < 40%, FEV1, FVC, DLCO (diffusion capacity) < 40% of predicted, LFT > 5 times the upper limit of normal, or creatinine clearance < 40 ml/min. • The evidence of HBV or HCV active infection (HBV DNA HCV RNA positive test). • Patients with HIV infection • Current uncontrolled infections • Patients with other life-threatening concurrent disease • Patients receiving strong CYP3A inducers (eg Carbamazepime, Phenytoin, Rifampicin), within seven days before the first dose of VEN-DEC combination. • Subjects with known hypersensitivity to any of the component medication • Subject has a history of other malignancies within 2 years prior to study entry, with the exception of: - Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; - Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; - Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. • Participation in another clinical trial within 1 month before the start of this trial.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 29 Jun 2021 | 100 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Dacogen 50 mg powder for concentrate for solution for infusion. | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION. | INTRAVENOUS USE | 20 | 56 | PRD3349065 |
Venclyxto 100 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL USE | 400 | 5 | PRD6353834 |