Venetoclax + CLAG-M for AML
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This multicenter, open-label phase II study combines CLAG-based therapy with or without venetoclax in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) in order to improve measurable residual disease (MRD) clearance and event-free survival. Investigators hypothesize that the addition of venetoclax to CLAG-M in patients with relapsed or refractory AML is safe, and superior to CLAG-M alone in improving patient outcomes.
Is the drug Venetoclax + CLAG-M a promising treatment for AML?Venetoclax is a drug that shows promise for treating certain types of leukemia, like chronic lymphocytic leukemia (CLL), with good response rates. However, its effectiveness for acute myeloid leukemia (AML) is less clear, especially in patients who have already tried other treatments. While it is used in combination with other drugs for AML, the success rates are not as high, and the overall survival time is relatively short. Therefore, while Venetoclax has potential, its promise for AML specifically is not as strong as for other types of leukemia.4891112
What safety data exists for Venetoclax + CLAG-M treatment in AML?The provided research does not contain safety data for Venetoclax + CLAG-M treatment in AML. It focuses on the safety of aprepitant, a different drug used for preventing chemotherapy-induced nausea and vomiting.12356
What data supports the idea that Venetoclax + CLAG-M for AML is an effective treatment?The available research shows that Venetoclax, when used in combination with other treatments, can be effective for patients with relapsed or refractory acute myeloid leukemia (AML). In one study, 76% of patients who survived more than two cycles of therapy achieved recovery of certain blood cells, and 52% achieved complete remission, meaning their cancer was no longer detectable. However, another study found that the complete remission rate was only 12.4% overall, but higher when combined with a specific drug called azacitidine. This suggests that while Venetoclax can be effective, its success may depend on the combination of treatments used. Compared to intensive chemotherapy, the effectiveness of Venetoclax combined with other treatments is still being studied, but it shows promise for some patients.47101113
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had recent venetoclax exposure within 3 months, and you must be off any AML-directed therapy for at least 14 days or five half-lives, whichever is shorter, before starting the trial. Immunosuppressive therapy is also restricted, except for low-dose prednisone.
Eligibility Criteria
This trial is for patients with acute myeloid leukemia (AML) that has come back or hasn't responded to treatment. Participants should be suitable for intensive chemotherapy. Specific details about inclusion and exclusion criteria are not provided, but typically these would involve age, previous treatments, and overall health status.Inclusion Criteria
My AML cancer has returned or is not responding to treatment.
I am between 18 and 80 years old.
I am HIV-positive, on treatment, and my viral load has been undetectable for 6 months.
I have chronic hepatitis B but it's under control with medication.
I can take care of myself but might not be able to do heavy physical work.
My AML developed from MDS and was treated before.
Exclusion Criteria
My leukemia has spread to my brain or spinal cord.
I had a stem cell transplant from a donor within the last 3 months.
My cancer has a known TP53 mutation.
I have another cancer besides AML that needs treatment.
I haven't taken strong immune-suppressing drugs in the last 2 weeks, except for low-dose prednisone or its equivalent.
I have been treated with a high-dose cytarabine regimen before.
I have heart problems that limit my use of certain cancer drugs.
Treatment Details
The study tests if adding a drug called Venetoclax to the CLAG-M regimen (a combination of Cladribine, Cytarabine, Mitoxantrone, G-CSF) is safe and more effective than CLAG-M alone in improving outcomes for relapsed or refractory AML patients.
2Treatment groups
Experimental Treatment
Active Control
Group I: CLAG-based therapy with venetoclaxExperimental Treatment2 Interventions
Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone) and Venetoclax
Group II: CLAG-based therapy without venetoclaxActive Control1 Intervention
Study participants will receive CLAG-M (cladribine, cytarabine, G-CSF, mitoxantrone)
Find a clinic near you
Research locations nearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
Dana-Farber Cancer InstituteBoston, MA
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Who is running the clinical trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
AbbVieIndustry Sponsor
References
Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. [2019]The neurokinin-1-receptor antagonist aprepitant, when given in combination with a corticosteroid and a 5-hydroxytryptamine type 3 (5-HT(3))-receptor antagonist, has been shown to be effective for the prevention of acute and delated chemotherapy-induced nausea and vomiting (CINV).
[Clinical usefulness of oral aprepitant for alleviation of delayed nausea and vomiting induced by mFOLFOX6--report of a case]. [2018]A 50-year-old-woman underwent high anterior resection for sigmoid colon adenocarcinoma. Modified oxaliplatin/l / -LV/ 5-FU(mFOLFOX6)was started as adjuvant treatment due to final-stage III b. Granisetron 3 mg and dexamethasone 8 mg for prophylaxis chemotherapy-induced nausea and vomiting (CINV) were administered intravenously 30 min before oxaliplatin administration. Grade 3 delayed CINV was observed at course 4. CINV could not be controlled by any rescue medications. We adopted a neurokinin-1 receptor antagonist (aprepitant) that alleviated the emetic effects of substance P. The oral aprepitant dose was 125 mg on day 1 and 80 mg on days 2 and 3. Afterward, delayed vomiting was completely controlled and chemotherapy could be continued to course 12. Aprepitant is a very active antiemetic drug for the prevention of delayed nausea and vomiting induced by mFOLFOX6 regimen.
Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial. [2018]Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]Venetoclax (Venclexta™) is a potent, selective, orally available, small-molecule B-cell lymphoma 2 inhibitor that achieves response rates of about 80% and has an acceptable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). .
Safety Profile of HTX-019 Administered as an Intravenous Push in Cancer Patients: A Retrospective Review. [2020]Label="INTRODUCTION">HTX-019 [CINVANTI® (aprepitant injectable emulsion)] is a neurokinin 1 receptor antagonist (NK-1 RA) approved as a 30-min infusion for preventing acute and delayed chemotherapy-induced nausea and vomiting. HTX-019 has been generally well tolerated when administered as a 30-min infusion or 2-min injection [intravenous (IV) push] in healthy subjects. This real-world analysis assesses safety of HTX-019 via IV push in patients with cancer and addresses a recent IV bag shortage.
Crossover safety study of aprepitant: 2-min injection vs 30-min infusion in cancer patients receiving emetogenic chemotherapy. [2020]Introduction: HTX-019 (CINVANTI®) is a novel injectable emulsion formulation of the neurokinin 1 receptor antagonist (RA) aprepitant, approved for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV). HTX-019 has demonstrated a tolerable safety profile when administered via 30-min intravenous (IV) infusion and 2-min IV injection in healthy volunteers. This prospective study evaluated the safety of HTX-019 administered via 30-min IV infusion and 2-min injection (IV push) in patients with cancer. Materials and methods: This prospective single-center, randomized, safety, 2-sequence, 2-period, crossover study evaluated HTX-019 130 mg within a guideline-recommended 3-drug regimen for CINV prophylaxis in patients receiving highly (HEC) or moderately emetogenic chemotherapy (MEC). Treatment-emergent adverse events (TEAEs) were assessed at 0-30 (primary endpoint), 30-60, and >60 mins (chemotherapy administration period) following the initiation of the HTX-019 administration, focusing on infusion-site adverse events and hypersensitivity reactions (dyspnea, anaphylaxis). Results: Among 135 patients (35 MEC, 100 HEC), the most common diagnoses were ovarian (32), lung (17), endometrial (17), and colorectal (15) cancer. Patients were randomized 1:1 to a 2-min injection and a 30-min infusion of HTX-019 (sequence AB or BA), followed by a 5-hydroxytryptamine type 3 RA IV (palonosetron 0.25 mg for 30 s or ondansetron 8-16 mg for 5-10 mins), dexamethasone IV (8-12 mg for 15 mins), and the chemotherapy regimen. Both administration methods were generally well tolerated. No TEAEs occurred within 30 mins after start of HTX-019 administration. All TEAEs occurred during chemotherapy administration; 2 patients experienced 2 TEAEs following injection, and 5 experienced 8 TEAEs following infusion. Three adverse events following infusion (2 dyspnea, 1 throat closing) were considered serious. No TEAEs were considered related to HTX-019. Conclusion: Short injection of HTX-019 has a tolerable safety profile in patients with cancer, and represents an alternative method of HTX-019 administration for CINV prevention.
Venetoclax is safe and efficacious in relapsed/refractory AML. [2021]Data from 11 Israeli centers, where venetoclax was used for relapsed/refractory AML after intensive chemotherapy, were retrospectively collected. During 2016-2019, forty patients were identified. Median age was 67 years (21-82), 60% males, median of 2(1-4) prior lines of treatment and 42% relapsed after allogeneic transplant. 62.5% of the patients received the venetoclax with hypomethylating agents and 22.5% with low dose cytarabine. Median follow-up was 5.5 months. Of the 29 patients who survived for more than two cycles of therapy, 22 (76%) achieved neutrophil recovery and 59% (n = 17) recovered also their platelet count. In 15 (52% of those who survived > 2 months), CR/CRi was confirmed by bone marrow examination. The median OS from venetoclax initiation of all the patients and of those who survived more than 2 months was 5.5 and 6.5 months, respectively. In conclusion, this study demonstrates that venetoclax is safe and active also in AML patients with advanced disease.
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]Venetoclax (Venclexta®; Venclyxto®) is a first-in-class, oral, selective inhibitor of B cell lymphoma 2 (BCL2). In several countries, including the USA and those of the EU, venetoclax is indicated in combination with obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). Approval was based on the results of the phase III CLL14 trial in patients with previously untreated CLL and co-existing conditions. In this study, fixed-duration (12 months) targeted treatment with venetoclax + obinutuzumab resulted in significantly longer progression-free survival (PFS; primary endpoint) relative to fixed-duration chemoimmunotherapy with chlorambucil + obinutuzumab. Venetoclax + obinutuzumab was also associated with significantly higher rates of undetectable minimal residual disease (MRD), complete response and overall response than chlorambucil + obinutuzumab. Improvements in clinical outcomes with venetoclax + obinutuzumab were maintained during long-term follow-up, when all patients had been off treatment for ≥ 2 years. No significant between-group difference was observed in overall survival (OS). Venetoclax had an acceptable tolerability profile. Notable adverse events such as grade 3 or 4 neutropenia can be managed with supportive therapy and venetoclax dose modifications. In conclusion, fixed-duration venetoclax + obinutuzumab represents an important chemotherapy-free first-line treatment option for patients with CLL, particularly those who are not fit enough to receive intensive chemoimmunotherapy.
Tumor lysis syndrome risk in outpatient versus inpatient administration of venetoclax and hypomethlators for acute myeloid leukemia. [2021]Venetoclax along with hypomethylating agents (HMAs) is the new standard therapy for older patients with acute myeloid leukemia (AML) not fit for intensive frontline induction chemotherapy. Venetoclax is associated with fatal episodes of tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL), and recommendations are for its initiation for CLL and AML in the inpatient setting with close monitoring. Herein, we evaluated the safety of outpatient venetoclax ramp up when given in addition to HMAs for the treatment of AML.
A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). [2022]Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML.
Use of Venetoclax in Patients with Relapsed or Refractory Acute Myeloid Leukemia: The PETHEMA Registry Experience. [2022]The effectiveness of venetoclax (VEN) in relapsed or refractory acute myeloid leukemia (RR-AML) has not been well established. This retrospective, multicenter, observational database studied the effectiveness of VEN in a cohort of 51 RR-AML patients and evaluated for predictors of response and overall survival (OS). The median age was 68 years, most were at high risk, 61% received ≥2 therapies for AML, 49% had received hypomethylating agents, and ECOG was ≥2 in 52%. Complete remission (CR) rate, including CR with incomplete hematological recovery (CRi), was 12.4%. Additionally, 10.4% experienced partial response (PR). The CR/CRi was higher in combination with azacitidine (AZA; 17.9%) than with decitabine (DEC; 6.7%) and low-dose cytarabine (LDAC; 0%). Mutated NPM1 was associated with increased CR/CRi. Median OS was 104 days (95% CI: 56-151). For the combination with AZA, DEC, and LDAC, median OS was 120 days, 104 days, and 69 days, respectively; p = 0.875. Treatment response and ECOG 0 influenced OS in a multivariate model. A total of 28% of patients required interruption of VEN because of toxicity. Our real-life series describes a marginal probability of CR/CRi and poor OS after VEN-based salvage. Patients included had very poor-risk features and were heavily pretreated. The small percentage of responders did not reach the median OS.
Practical Management of the Venetoclax-Treated Patient in Chronic Lymphocytic Leukemia and Acute Myeloid Leukemia. [2022]Venetoclax is a potent oral, highly selective small-molecule inhibitor of the antiapoptotic B-cell lymphoma 2 protein approved for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma in treatment-naive patients (in combination with obinutuzumab) or for patients with relapsed/refractory CLL (in combination with rituximab). Venetoclax, in combination with azacitidine, decitabine, or low-dose cytarabine, is also approved in the United States for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are ≥ 75 years or have comorbidities that preclude use of intensive induction chemotherapy. Clinical studies of patients with CLL or AML report both hematologic (e.g., neutropenia) and nonhematologic (e.g., gastrointestinal disorders and tumor lysis syndrome) adverse events associated with administration of venetoclax. It is therefore essential to provide information on the appropriate management of venetoclax-associated side effects. This article discusses the efficacy and safety of venetoclax administration and presents strategies specifically for the management of neutropenia and certain nonhematologic adverse events in patients receiving venetoclax for the treatment of AML and CLL.
Outpatient initiation of venetoclax in patients with acute myeloid leukemia. [2023]Venetoclax is a treatment option in patients with acute myeloid leukemia (AML) in both the front-line and relapsed/refractory settings. Initiation of therapy has been previously restricted to the inpatient setting at some institutions due to a risk of tumor lysis syndrome (TLS) and limitations in medication access efficiency given the high cost of therapy.