Nintedanib and Azacitidine in Treating Participants With HOX Gene Overexpression Relapsed or Refractory Acute Myeloid Leukemia

NCT03513484 | Active Not Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: NU 17H04NCI-2018-00483STU00206525P30CA060553
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find the appropriate dose of the study drug nintedanib when combined with azacitidine and the associated side effects of the combination in older adults with AML characterized by HOX gene overexpression who are not interested in or not considered fit for standard intensive chemotherapy. The use of the study drug nintedanib in this study is investigational. Investigational means that this medication has not yet been approved by the FDA to treat this type of cancer. Azacitidine received FDA Approval in 2004 for myelodysplastic syndrome (a blood cancer related to AML) and has a National Comprehensive Cancer Network (NCCN) guideline recommendation for treatment of older adults who are not candidates for or decline intensive remission induction therapy. We expect participation to continue in this study based on each participant's response to the drug, and ability to tolerate treatment. Participants may continue to receive study treatments for 6 cycles (one cycle is 28 days long). If the 6 cycles of treatment is completed, participants may be moved on to a maintenance phase of treatment. Treatment will continue until the participant's leukemia gets worse, or they experience serious side effects, have a break in treatment for more than 56 days or the study doctor feels it is best for study treatments to stop.

Conditions

Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Fibroblast Growth Factor Basic Form Measurement; FLT3 Internal Tandem Duplication; Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Will be defined as the highest dose that causes dose limiting toxicities (DLTs) in \< 2 of 6 patients.

  Up to 28 days

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 24 months

• Overall survival

  Up to 24 months

• Complete remission (CR) rate

  Up to 24 months

Study Arms (1)

Treatment (nintedanib, azacitidine)

EXPERIMENTAL

Participants receive nintedanib PO BID on days 1-28 and azacitidine IV or SC on days 1-7. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, participants may discontinue treatment, receive nintedanib every 4-8 weeks, or receive nintedanib and azacitidine every 4-8 weeks.

Drug: Azacitidine; Other: Laboratory Biomarker Analysis; Drug: Nintedanib

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (nintedanib, azacitidine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nintedanib, azacitidine)

Nintedanib DRUG

Given PO

Also known as: BIBF 1120, BIBF-1120, Intedanib, Multitargeted Tyrosine Kinase Inhibitor BIBF 1120, tyrosine kinase inhibitor BIBF 1120, Vargatef

Treatment (nintedanib, azacitidine)

Eligibility Criteria

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

You may qualify if:

• ESCLATION COHORT: Patients must have a diagnosis of newly diagnosed and/ or relapsed/refractory AML with any of the following:
• Confirmed translocation involving 11q23
• Partial tandem duplication(PTD) of the MLL gene (on 11q23)
• FLT3-ITD (internal tandem duplication)
• Increased Fgf2 in serum (2 standard deviations above control serum samples)
• HOX(A9/A10) over-expression in bone marrow ( 2 standard deviations above control values in CD34+ cells from normal subjects)
• Note: Relapsed or refractory AML is defined as either:
• Recurrence of disease after a complete remission (CR), or
• Failure to achieve CR with initial therapy
• EXPANSION COHORT: Patients must have a diagnosis of newly diagnosed AML with any of the following:
• Confirmed translocation involving 11q23
• Partial tandem duplication (PTD) of the MLL gene (on 11q23)
• FLT3-ITD (internal tandem duplication)
• Increased Fgf2 in serum (2 standard deviations above control serum samples)
• HOX(A9/A10) over-expression in bone marrow (2 standard deviations above control values in CD34+ cells from normal subjects)

You may not qualify if:

• Patients who have received chemo-, hormone-, radio or immunotherapy or therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past 14 days prior to start of treatment or those who have not recovered from adverse events attributed to the agent to grade 1 or baseline
• Exceptions for prior treatments are:
• Hydroxyurea for increased blast count (no washout period required; it can be continued throughout the first cycle of therapy)
• Leukapheresis for leukocytosis (no wash out period required; it can be continued during the study)
• Note: If patient is registered prior to completion of washout, start date of treatment will need to be confirmed prior to registration; please see assigned quality assurance monitor (QAM) with questions
• Patients who have received any other investigational product within14 days of treatment are not eligible for this study; a wash out period ? 14 days or 5 half- lives (whichever is greater) is required from investigational treatment, prior to start of study treatment; please Note:
• If patient is registered prior to completion of washout, start date of treatment will need to be confirmed prior to registration; please see assigned QAM with questions
• The ?5 half-lives? time period will be determined by investigational pharmacy
• If half life is not known and cannot be predicted, then wash out of ? 14 days is required
• Patients who have had major injuries and/or surgery within the past 4 weeks (\< 28 days) prior to registration with incomplete wound healing and/or planned surgery while the patient is on study treatment
• Patients who have proteinuria CTCAE version (v)4.03 grade 2 or greater within \< 30 days of registration
• Patients who have significant cardiovascular diseases are not eligible; these are:
• Uncontrolled hypertension
• Unstable angina
• History of infarction within the past 12 months prior to start of study treatment

Sponsors & Collaborators

• Northwestern University: lead
• Robert H. Lurie Cancer Center: collaborator
• Boehringer Ingelheim: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; nintedanib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jessica Altman

  Northwestern University

  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: April 19, 2018
• First Posted: May 1, 2018
• Study Start: November 14, 2018
• Primary Completion: December 11, 2023
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 21, 2025

Record last verified: 2025-10

Locations

US (1)