Navitoclax, Venetoclax, and Decitabine for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia Previously Treated With Venetoclax

NCT05222984 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 22178NCI-2021-0555220398P30CA033572
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial is to find the side effect and best dose of navitoclax when given together with venetoclax and decitabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory) after previous treatment with venetoclax. Chemotherapy drugs, such as navitoclax, venetoclax, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Conditions

Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Will be assessed and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0.

  Up to 1 year

Secondary Outcomes (4)

• Overall response rate

  Up to 1 year

• Progression Free Survival (PFS)

  Assessed up to 1 year

• Overall Survival (OS)

  Assessed up to 1 year

• Dose Limiting Toxicity (DLT)

  Up to 35 days (1 cycle)

Other Outcomes (2)

• Change in percent blasts in bone marrow

  Baseline up to 1 year

• Change in percent blasts in peripheral blood

  Baseline up to 1 year

Study Arms (1)

Treatment (navitoclax, venetoclax, decitabine)

EXPERIMENTAL

Patients receive venetoclax PO QD and navitoclax PO QD on days 1-35, and decitabine IV over 1 hour on days 8-12 of cycle 1. Starting on cycle 2, patients receive venetoclax PO QD and navitoclax PO QD on days 1-28, and decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Decitabine; Biological: Navitoclax; Drug: Venetoclax

Interventions

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (navitoclax, venetoclax, decitabine)

Navitoclax BIOLOGICAL

Given PO

Also known as: A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

Treatment (navitoclax, venetoclax, decitabine)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (navitoclax, venetoclax, decitabine)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• For participants under the age of 18 years, documentation of adolescent assent by the participant and consent of both parents or guardian
• Adults aged \>= 18 years
• Adolescent patients aged \>= 16 years and \< 18 years weighing at least 45 kg who have no other standard-of-care option for treatment
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Patients with histologically confirmed AML, according to World Health Organization (WHO) criteria, with refractory/relapsed (R/R) disease following a venetoclax-containing regimen who are ineligible for therapies known to be effective for treatment of their AML.
• Patients with extramedullary disease may be included if they also have marrow involvement
• Patients with acute promyelocytic leukemia (APL) will not be eligible
• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 of prior anti-cancer therapy
• Ability to swallow pills
• Absolute neutrophil count (ANC) \>= 750/mm\^3 (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
• White blood cell (WBC) =\< 25 x 10\^9/L prior to initiation of study therapy. Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may be required (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• Platelets \>= 75,000/mm\^3
• NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement

You may not qualify if:

• Hematopoietic stem cell transplant within 100 days prior to day 1 of protocol therapy
• Chemotherapy, radiation therapy, biological therapy, or immunotherapy within 14 days or 5 half-lives, whichever is shorter, prior to day 1 of protocol therapy with the following exceptions:
• Subjects will be allowed to have been on venetoclax at screening and remain on it through treatment start.
• Hydroxyurea is allowed prior to treatment and through cycle 1 for control of rapidly progressing leukemia
• Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of protocol therapy
• Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit consumed within 3 days prior to the first dose of study drug
• Immunosuppressants (steroids =\< 10 mg/day of oral prednisone or equivalent is allowed) within the last 28 days
• Hematopoietic growth factors in the last 14 days
• Must not have received or planning to receive live vaccine while being on study or 4 weeks before and after completion of treatment
• Herbal medications known to affect platelet function within 14 days of therapy initiation
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Active graft-versus-host-disease (GVHD)
• Active central nervous system (CNS) disease
• No measurable disease in the bone marrow
• Active diarrhea

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; Injections; navitoclax; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Anthony Stein, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 3, 2022
• Study Start: July 29, 2022
• Primary Completion (Estimated): March 2, 2027
• Study Completion (Estimated): March 2, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)