Azacitidine (AZA) in Minimal Residual Disease (MRD) Chronic Myeloid Leukemia (CML)

NCT01460498 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2011-0254NCI-2011-03531
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a 2 part study. The goal of the first part of this clinical research study is to find the highest tolerable dose of azacitidine that can be given with a TKI that you are already taking (such as Gleevec, Sprycel, or Tasigna). The safety of this drug will also be studied. The goal of the second part is to see if this combination may improve your response to the TKI you are already taking. Azacitidine is designed to change genes that are thought to cause leukemia. By changing these genes, the drug may help to stop them from causing the disease to grow.

Conditions

Leukemia

Keywords

Leukemia; Chronic Myeloid Leukemia; CML; Complete cytogenetic remission; CCyR; Minimal residual disease; Philadelphia chromosome (Ph)-; BCR/ABL-positive; Tyrosine kinase inhibitor; TKI; Azacitidine; 5-Azacytidine; 5-AZA; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Azacitidine

  MTD is defined as the highest dose level in which 6 patients have been treated and one or fewer patient experiences Dose-Limiting Toxicity (DLT) within the first course of treatment.

  First 28 day cycle

• Number of Participants with Decrease of Transcript Levels by at Least One Log (or Undetectable Transcript Level) Within 12 Months

  Participants with response defined as a greater than a one-log reduction of BCR-ABL transcript levels from the baseline level at the time vaccination was initiated, or a disappearance of BCR-ABL transcripts (i.e., complete molecular response) within 12 months.

  Baseline to 12 months

Study Arms (2)

Dose Escalation Group (AZA)

EXPERIMENTAL

Azacitidine (AZA) starting dose 50 mg/m2 a day for 3 days subcutaneous or intravenous of 28 day cycle. TKI at dose received during last 6 months.

Drug: Azacitidine (AZA); Drug: Tyrosine kinase inhibitor (TKI)

Expansion Group (AZA MTD)

EXPERIMENTAL

Dose Escalation Group plus additional 36 participants for Azacitidine 75 mg/m2 (or Phase I MTD) either subcutaneous or intravenous every day for 3 days of 28 day cycle. TKI at dose received during last 6 months.

Drug: Tyrosine kinase inhibitor (TKI); Drug: Azacitidine

Interventions

Azacitidine (AZA) DRUG

Starting Dose 50 mg/m2 by subcutaneous or by vein for 3 days of a 28 day cycle.

Also known as: 5-Azacytidine, 5-AZA, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816

Dose Escalation Group (AZA)

Tyrosine kinase inhibitor (TKI) DRUG

Continuation of dose already receiving during previous 6 months.

Dose Escalation Group (AZA); Expansion Group (AZA MTD)

Azacitidine DRUG

75 mg/m2 daily for 3 days, unless MTD defined at lower dose level in Phase I then that would become dose used for Phase II.

Also known as: 5-Azacytidine, 5-AZA, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816

Expansion Group (AZA MTD)

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:

• Patients 16 years or older with Philadelphia chromosome (Ph)- or BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR).
• Patients must have received FDA-approved TKI therapy for at least 18 months and not have increased their dose of FDA-approved TKI in the last 6 months. Patients participating on frontline protocols 2005-0048 (nilotinib) and 2005-0422 (dasatinib) are eligible for enrollment on this study.
• Phase II patients must be in complete cytogenetic remission. For the phase I portion of the study, patients may be included without a complete cytogenetic remission provided they are in chronic phase.
• Phase II patients must have detectable BCR-ABL transcript levels meeting at least one of the following criteria: Patient has never achieved a major molecular response, and transcript levels have shown in at least two consecutive measures separated by at least 1 month to have increased by any value, or Achieved a major molecular response that has been lost with an increase in transcript levels by at least 1-log, confirmed in two consecutive analyses separated by at least 1 month, or The patient has received therapy for at least 2 years and does not have a sustained major molecular response, or The patient has received therapy for at least 5 years and does not have a sustained complete molecular response. Patients included in the phase I portion of the study are eligible regardless of their level of BCR-ABL transcripts.
• Patients must not have had a known continuous interruption of imatinib therapy of greater than 14 days or for a total of 6 weeks in the 6 months prior to enrollment.
• Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
• ECOG performance status \</= 2.
• Adequate organ function defined as: bilirubin \< 2x upper limit of normal (ULN) (unless associated with Gilbert's syndrome), and ALT or AST \</= 2.5x ULN.
• ANC \>/=1 x10(9)/L and platelets \>/= 50 x10(9)/L.
• Serum creatinine \< 1.8 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\*. Males(mL/min):(140-age)\* ABW(kg) / 72\* (serum creatinine(mg/dl)); Females (mL/min):0.85\*(140-age)\* ABW(kg) / 72\*(serum creatinine (mg/dl))
• Women of childbearing potential should be advised to avoid becoming pregnant and practice effective methods of contraception. Men should be advised not to father a child while receiving treatment with azacitidine. Azacitidine is classified as Pregnancy Category D. Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation. Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study.
• Women of childbearing potential should have a pregnancy test within 7 days before initiation of study drug.

You may not qualify if:

• Patients receiving any other investigational agents.
• Patients who are pregnant or breast-feeding.
• Patients with clinically significant heart disease (NYHA Class III or IV).
• Known or suspected hypersensitivity to azacitidine or mannitol.
• Patients with advanced malignant hepatic tumors.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Celgene Corporation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasm, Residual; Philadelphia Chromosome

Interventions

Azacitidine; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 24, 2011
• First Posted: October 27, 2011
• Study Start: August 8, 2012
• Primary Completion: August 7, 2019
• Study Completion: August 7, 2019
• Last Updated: March 5, 2020

Record last verified: 2020-03

Locations

US (1)