Efficacy of Low-dose Venetoclax With Itraconazole + TACL for R/R ALL Patients

NCT07039877 | Recruiting Phase 2

• 1 other identifier: HE25-00004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Relapsed/refractory acute lymphoblastic leukemia remains a challenge in the context of limited access to immunotherapy in developing countries. With such poor 5-year overall survival rates of 10%, the investigators need strategies that surpass the complete response rate achieved in this setting, which does not exceed 60% effectiveness with different regimens, and to eventually transfer patients to hematopoietic stem cell transplantation. In this context, the investigators are studyng if the use of venetoclax, a BCL2 inhibitor, with the use of a cytochrome p450 inhibitor such as itraconazole, alongside the TACL chemotherapy regimen, which is based on the combination of asparaginase, dexamethasone, bortezomib, vincristine, and mitoxantrone.

Conditions

Acute Lymphobkastic Leukemia; Acute Lymphoblastic Leukaemia Recurrent; Philadelphia Chromosome Negative ALL

Keywords

ALL; relapsed ALL; Venetoclax; TACL; refractoy ALL

Outcome Measures

Primary Outcomes (1)

• Overall response rata after low dose venetoclax with itraconazole plus TACL

  To evaluate the overall response after reinduction to remission with low dose venetoclax plus TACL in patients with relapsed/refractory acute lymphoblastic leukemia

  16 months

Secondary Outcomes (5)

• Percentage of measurable residual disease in complete response

  16 months

• Adverse events evaluatio

  16 months

• Patients recieving HSCT after chemotherapy

  24 months

• Event-free survival

  24 months

• Overall survival

  24 months

Study Arms (1)

TACL plus low dose Venetoclax and Itraconazole

EXPERIMENTAL

Salvage chemotherapy will be assigned as follows: * Venetoclax 100 mg orally every day for 7 days * Itraconazole 100 mg orally every 12 hours for 7 days * Vincristine 1.4 mg/m2 intravenously on days 1, 8, 15, and 22 * Mitoxantrone 6 mg/m2 intravenously on day 1 * L-Asparaginase 6,000 IU/m2 intramuscularly on days 5, 7, 9, 11, 13, 16, 18, 20, and 23 * Dexamethasone 16 mg orally from days 1 to 15 * Bortezomib 2 mg subcutaneously on days 1, 4, 8, and 11 * Rituximab 375 mg/m2 intravenously on day 8 for patients with CD20+, more than 20% expression * Intrathecal Chemotherapy or CNS (-): Days 8 and 15 or CNS (+): Days 1, 8, 15, and 22

Drug: Venetoclax low dose with itraconazole

Interventions

Venetoclax low dose with itraconazole DRUG

The investigators will add venetoclax in low dose (100 mg) with itraconazole to the pediatric inspired regimen TACL to enchance the complete response rate

TACL plus low dose Venetoclax and Itraconazole

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• B-cell or T-cell acute lymphoblastic leukemia.
• Philadelphia chromosome negative
• Relapsed disease after any line of treatment, defined as detection of disease activity at any time after remission
• Refractory disease after first-line treatment, defined as: more than 5% blasts after completion of induction/consolidation by flow cytometry
• Not having included venetoclax in any prior regimen.
• No prior organ damage, defined as the absence of any serious, life-threatening disease prior to the start of treatment.
• Performance status defined by the ECOG scale between 0 and 2.

You may not qualify if:

• Isolated CNS relapse.
• Performance status defined by ECOG scale between 3 and 4.
• CTCAE-classified sensory or motor neuropathy of grade 3 or higher.
• History of hypersensitivity or intolerance to the drugs included in the regimen.
• Prior organ damage, defined as the presence of any serious, life-threatening illness prior to the start of treatment.

Sponsors & Collaborators

• Hospital Universitario Dr. Jose E. Gonzalez: lead

Study Sites (1)

Hospital Universitario Dr. Jose E. Gonzalez

Monterrey, Nuevo León, 64360, Mexico

RECRUITING

Related Publications (1)

• Colunga-Pedraza JE, Gonzalez-Llano O, Gonzalez-Martinez CE, Gomez-Almaguer D, Yanez-Reyes JM, Jimenez-Antolinez V, Colunga-Pedraza PR. Outpatient low toxic regimen with bortezomib in relapsed/refractory acute lymphoblastic leukemia in pediatrics and AYA patients: Single-center Mexican experience. Pediatr Blood Cancer. 2020 May;67(5):e28241. doi: 10.1002/pbc.28241. Epub 2020 Mar 11.

  PMID: 32159276 BACKGROUND

MeSH Terms

Interventions

venetoclax; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Central Study Contacts

Andres Gomez-De Leon, Professor of Hematology

CONTACT

+528116089404; drgomezdeleon@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hematology

Model Details: One arm, open-label, phase 2 study

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: June 26, 2025
• Study Start: January 2, 2025
• Primary Completion: February 28, 2026
• Study Completion: April 30, 2026
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

ME (1)