Addition of venetoclax to standard chemotherapy with cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia (AML)

Phase 1

• Conditions: Patients 18-75 years with acute myeloid leukaemia (AML) at first or second relapse after intensive chemotherapy including allogeneic stem cell transplantation or primary refractory to standard induction chemotherapy who are eligible for intensive salvage treatment; MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-003025-28-DE
• Lead Sponsor: Technische Universität Dresden

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-01-29
• Last Update Posted: 4 March 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

• Signed Informed consent
• AML according to WHO criteria, excluding APL
• Relapsed after first or second CR, including relapse after allogeneic stem cell transplantation (dose escalation and expansion phase)
• Only expansion phase: Primary refractory after 1-2 cycles of standard induction chemotherapy (100 to 200 mg/m2 cytarabine over 7-10 days plus anthracycline or mitoxantrone over 3 days) or equivalent treatment (e.g. CPX351)
Note: Primary refractory disease is defined by either = 20% myeloid blasts on early response assessment around day 15 after start of the most recent induction, or by = 5% myeloid blasts after blood count recovery after start of the most recent induction, respectively.
• Age 18-75 years
• Fit for intensive chemotherapy, defined by
- ECOG 0-2, life expectancy > 3 months
- Adequate hepatic function (ALAT/ASAT/Bilirubin =2.5 x ULN )
- Adequate renal function assessed by creatinine < 1.5 x ULN OR creatinine clearance (by Cockcroft Gault Formula) = 50 mL/min
• Patient is afebrile and hemodynamically stable for at least 72 hours at the time of study medication initiation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 54

Exclusion Criteria

• Acute promyelocytic leukemia
• CNS involvement or subjects with extramedullary disease only
• Known hypersensitivity to any agent given in association with this study including cytarabine or mitoxantrone
• relapse within 90 days after last cytarabine dose
• Intended hematopoietic stem cell transplantation planned as early conditioning from aplasia without previous blood count recovery
• Cumulative previous exposure to anthracyclines of >410 mg/m2 doxorubicin equivalents
• Acute GVHD = grade 2, extensive chronic GVHD or requiring systemic immunosuppressive therapy
• HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism based lymphopenia that may potentially increase the risk of opportunistic infections)
• Inability to swallow oral medications
• Any malabsorption condition
• Cardiovascular disability status of New York Heart Association Class = 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
• Chronic respiratory disease that requires continuous oxygen use.
• White blood cell count > 25 × 109/L. Note: Hydroxyurea is permitted to meet this criterion.
• AML relapse treatment with any investigational or commercial drug within 10 days before enrolment. Hydroxyurea is allowed until enrolment to control peripheral WBC counts.
• Substance abuse, medical, psychological, or social conditions that may interfere with the subject’s cooperation with the requirements of the trial or evaluation of the study results
• Acute non-hematologic toxicities from any prior anti-leukemia therapy or from previous investigational drugs that have not resolved to Grade <2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
• History of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (Occult or prior hepatitis B virus (HBV) infection (defined as negative hepatitis B surface antigen and positive total hepatitis B core antibody) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody after vaccination or prior but cured hepatitis B are eligible. Patients positive for hepatitis C virus antibody are eligible provided PCR is negative for HCV RNA)
• History of clinically significant liver cirrhosis (e.g., Child-Pugh class B and C).
• Pregnant or breastfeeding patients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified