Pioglitazone and Tyrosine Kinase Inhibitor in Treating Patients With Relapsed Chronic Myeloid Leukemia

NCT02730195 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB00086670NCI-2016-00248Winship3121-15
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pioglitazone hydrochloride and tyrosine kinase inhibitor (TKI) therapy works in treating patients with chronic myeloid leukemia (CML) that has come back after a period of improvement (relapsed) after a first TKI discontinuation. TKI may stop the growth of cancer cells by blocking certain enzymes need for cell growth. Although TKI therapies are effective against CML, there are residual cancer cells called leukemia stem cells that are able to hide from TKIs. Pioglitazone is a drug approved by the Food and Drug Administration to treat diabetes and has been shown in laboratory studies to increase CML stem cell death when given together with TKI therapy. Giving pioglitazone with TKI therapy may be effective in treating patients with CML.

Conditions

Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AEs), Graded According to Common Terminology Criteria for Adverse Events Version 4.03

  The AE incidence will be described. An AE is any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product which does not necessarily have to have a causal relationship with this treatment. AEs will be assessed through scheduled assessments and subject reported diaries.

  Up to 30 days after the end of treatment

• Proportion of Subjects Who Achieve and Maintain Major Molecular Response (MMR) Following a Second Discontinuation of TKI Using Blood Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) for Breakpoint Cluster Region-Abelson1 (BCR-ABL1)

  The proportion of subjects that has reappearance of BCR-ABL1 will be described. Descriptive statistics that will summarize the changes in BCR-ABL1 testing over time will be presented. Subgroup analyses will be performed by baseline potential prognostic factors. Subgroups will include: age, gender, race, underlying diagnosis, and other disease-related prognostic factors (disease status).

  Up to 6 months

Secondary Outcomes (1)

• Proportion of Subjects Who Lose MMR Following Discontinuation of Pioglitazone and TKI Using Blood qRT-PCR for BCR-ABL1

  Up to 3 years

Study Arms (1)

Pioglitazone & TKI therapy

EXPERIMENTAL

Patients receive pioglitazone PO QD on days 1-28. Patients also start or continue the same tyrosine kinase inhibitor (TKI) therapy at the pre-discontinuation doses. Courses repeat every 28 days for 6 months in the absence of disease progression or unacceptable toxicity.

Drug: Pioglitazone; Drug: Tyrosine Kinase Inhibitor (TKI)

Interventions

Pioglitazone DRUG

Given PO

Also known as: Actos, Pioglitazone Hydrochloride

Pioglitazone & TKI therapy

Tyrosine Kinase Inhibitor (TKI) DRUG

Given TKI therapy

Also known as: Protein Tyrosine Kinase Inhibitors, PTK Inhibitors, TK Inhibitors

Pioglitazone & TKI therapy

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:

• Chronic myeloid leukemia (CML) in any phase
• Philadelphia chromosome positive acute lymphoblastic leukemia
• Loss of major molecular response (MMR) following a first TKI discontinuation trial
• Serum bilirubin \< 1.5 x upper limit of normal values
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal values
• Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period; women of child bearing potential must have a negative urine pregnancy test at the time of enrollment; acceptable methods of birth control include oral contraceptive, intrauterine device, transdermal/implanted or injected contraceptives and abstinence
• Males must agree to abstain from sexual activity or agree to utilize a medically-approved contraception method during and for 3 months after the treatment period
• Patient requiring anti-diabetic medications to manage hyperglycemia are eligible. Adjustments of other anti-diabetic agents will be made with close monitoring of blood glucose
• Informed consent
• Be able and willing to comply with study visits and procedures

You may not qualify if:

• Known loss of complete cytogenetic response (CCyR) by marrow cytogenetic or blood fluorescence in situ hybridization (FISH) for breakpoint cluster region (BCR)- v-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1)
• Loss of complete hematologic response (CHR)
• Participation in another clinical trial with any investigative drug within 30 days prior to study enrollment
• Chronic graft-versus-host disease requiring systemic immunosuppression post-allogeneic hematopoietic stem cell transplantation
• Cardiovascular disease: history of congestive heart failure, myocardial infarction in the 6 months preceding study entry, symptomatic cardiac arrhythmia requiring treatment
• History of bladder cancer
• Gross (visible) hematuria
• Known history of osteoporosis
• Known history of macular edema
• Known history of ABL1-domain mutation that predicts resistance to the discontinued TKI
• Significant medical or psychiatric disorder that would interfere with consent, study participation, or follow-up
• Known allergy to pioglitazone
• Pregnant or breastfeeding
• Use of thiazolidinedione (TZD) within 28 days prior to enrollment
• Significant gastrointestinal condition that could potentially impair the absorption or disposition of the drug

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Pioglitazone; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

Study was terminated early due to previous principal investigator leaving institution.

Results Point of Contact

• Title: William Blum, MD
• Organization: Emory University

william.g.blum@emory.edu

404-778-1900

Study Officials

• William Blum, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Principal Investigator

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 6, 2016
• Study Start: May 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: January 9, 2019
• Results First Posted: January 9, 2019

Record last verified: 2018-12

Locations

US (1)