The Use of Decitabine as Induction Therapy for Acute Myeloid Leukemia With Complex and/or Monosomal Karyotype

NCT03080766 | Unknown Phase 2 DMC

• 1 other identifier: AML002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Acute myeloid leukemia (AML) is a heterogeneous group of diseases with distinct clinicopathologic features sharing in common an abnormal increase in myeloblasts in blood and bone marrow (BM). In about 5-10% patients, the myeloblasts exhibit chromosomal abnormalities (complex and/or monosomal karyotype, CK/MK\*) that are associated with refractoriness to conventional chemotherapy and an extremely bad prognosis. Standard induction chemotherapy for AML comprises daunorubicin and cytarabine, the "7+3" regimen. However, treatment is largely ineffective for CK/MK AML with a temporary clearance of blasts achieved in only 30-40% cases and the cumulative toxicities resulting from repeated courses of chemotherapy have significantly increased the morbidity and mortality risks in subsequent allogeneic BMT. Therefore, standard treatment is unsatisfactory and there is an unmet clinical need for more effective and less toxic induction regimen. Both previous and recent studies showed that 10 day course of decitabine (20 mg/m2/day) induced remission in 70-100% patients with CK/MK AML, particularly those with TP53 mutations. In this study, patients with CK/MK AML will be treated with decitabine to induce remission. Bone marrow examination will be performed after each course until complete clearance of blasts or disease progression. Patients achieving CR/CRi (see below) will continue to receive 4 more courses, after which patients eligible for BMT and for whom donors are available will receive curative BMT. We reckon that the time it takes for 4 courses of decitabine will suffice for transplantation workup in HK. . Patients ineligible for BMT will continue to receive decitabine until leukemia progression. The response rate, leukemia free survival (LFS), overall survival (OS) and percentage of patients who can be bridged to BMT will be compared with historical 7+3 regimen control.

Conditions

Acute Myeloid Leukemia; Complex Karyotype

Outcome Measures

Primary Outcomes (1)

• Complete remission (CR):

  No increase in blasts in BM or PB (\<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L.

  up to 16 weeks

Study Arms (1)

decitabine

EXPERIMENTAL

Decitabine is a white to almost white powder for concentrate for solution for infusion. It is supplied as a lyophilized preparation in a clear colorless 20ml glass vial containing 50 mg decitabine. The concentrate should be aseptically reconstituted with 10 ml of water for injections. After reconstitution, the concentrate must be diluted within 15 minutes using cooled infusion fluids and completely administered to patients within 5 hours. The drug will then be administrated intravenously. Dosage 20 mg/m2 28-day course, for each course, receive decitabine for 10 days

Drug: Decitabine

Interventions

Decitabine DRUG

Decitabine (trade name Dacogen®) is a cytidine deoxynucleoside analogue, which selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation that can result in reactivation of tumor suppressor genes, induction of cellular differentiation or cellular senescence followed by programmed cell death.

Also known as: Dacogen

decitabine

Eligibility Criteria

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

You may qualify if:

• Adult patients (age 18-65 years old) with CK/MK AML at diagnosis
• De novo or secondary AML is allowed
• ECOG performance ≤ 2
• Subjects with adequate liver, pancreatic and renal function at screening as demonstrated by :Direct bilirubin \< 2 x upper limit of laboratory normal (ULN) Alanine aminotransferase (ALT) \< 2.5 x ULN MDRD-eGRF \> 30ml/min/1.73m2
• Negative serum / urine pregnancy test within 7 days before starting study treatment in women with childbearing potential.
• Subjects with ability to understand the protocol and signed a written informed consent document prior to the participation of the study.

You may not qualify if:

• Patients with CK/MK AML who have received standard induction chemotherapy before
• Patients with active and uncontrolled infection.
• Patients with concurrent severe and uncontrolled concomitant medical conditions that could cause unacceptable safety risk or compromise compliance with the protocol.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Janssen, LP: collaborator

Study Sites (1)

The University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine

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

Study Officials

• Anskar Leung, Professor

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Crosby Lu, SC

CONTACT

852-22554361; khlu@hku.hk

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: Clinical Professor

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: March 15, 2017
• Study Start: March 1, 2017
• Primary Completion: September 30, 2021
• Study Completion: December 28, 2021
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

HK (1)