Guadecitabine With or Without Idarubicin or Cladribine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

NCT02096055 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2013-0843NCI-2014-00981
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial studies how well guadecitabine with or without idarubicin or cladribine works in treating older patients with previously untreated acute myeloid leukemia. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cladribine, 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. It is not yet known whether guadecitabine with or without idarubicin or cladribine is more effective in treating older patients with previously untreated acute myeloid leukemia.

Conditions

Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (5)

• Number of Participants With a Complete Response

  Complete Response = Complete Remission (CR) + Complete Remission without blood count recovery (CRi) - CR: Neutrophil count \>/= 1.0 x 10\^9/L and platelet count \>/= 100 x 10\^9/L, and normal bone marrow differential (\</+ 5% blasts). (CRi): Peripheral blood and bonemarrow results as for CR, but with platelet counts of \< 100 x 109/L or ANC \< 1.0 x 109/L

  Up to 4 years, 3 months

• Remission Duration

  The date of Complete Response to the date of loss of response or last follow-up.

  Up to 4 years, 3 months

• Leukemia-free Survival

  Survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups. Time from date of treatment start until the date of first objective documentation of disease-relapse.

  Up to 4 years, 3 months

• Survival

  Survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups.

  Up to 4 years, 3 months

• Number of Participants With the Most Frequently Reports Grade 3 or 4 Adverse Event.

  The most frequently reported adverse events will be determined by the Principal Investigator. The number of participants who experienced the most frequent grade 3 or 4 adverse events will be reported.

  Up to 4 years, 3 months

Study Arms (4)

Arm I (guadecitabine)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-5. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine as in Induction therapy. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Guadecitabine

Arm II (CLOSED) (guadecitabine)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-10. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC on days 1-5 (days 1-10 of courses 1 and 2). Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Guadecitabine

Arm III (guadecitabine, idarubicin)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive guadecitabine SC on days 1-5 and idarubicin IV over up to 1 hour on days 1-2. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC on days 1-5 and idarubicin IV over up to 1 hour on day 1. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Guadecitabine; Drug: Idarubicin

Arm IV (CLOSED) (guadecitabine, cladribine)

EXPERIMENTAL

INDUCTION THERPAY: Patients receive guadecitabine SC and cladribine IV over up to 1 hour on days 1-5. Courses repeat every 4-6 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a CR or CRp continue on to Maintenance therapy; patients not achieving CR or CRi but deriving clinical benefit may continue to Maintenance therapy at the discretion of the PI. MAINTENANCE THERAPY: Patients receive guadecitabine SC and cladribine IV over up to 1 hour on days 1-5. Courses repeat every 4-8 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Cladribine; Drug: Guadecitabine

Interventions

Cladribine DRUG

Given IV

Also known as: 2-CdA, 2CDA, CdA, Cladribina, Leustat, Leustatin, Leustatine, RWJ-26251

Arm IV (CLOSED) (guadecitabine, cladribine)

Guadecitabine DRUG

Given SC

Also known as: DNMT inhibitor SGI-110, S110, SGI-110

Arm I (guadecitabine); Arm II (CLOSED) (guadecitabine); Arm III (guadecitabine, idarubicin); Arm IV (CLOSED) (guadecitabine, cladribine)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

Arm III (guadecitabine, idarubicin)

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Previously untreated AML patients, except those who have received prior therapy with hydroxyurea, single agent chemotherapy (e.g. decitabine), hematopoietic growth factors, biological or targeted therapies are allowed
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Sign a written informed consent form
• Total bilirubin =\< 2 mg/dL
• Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) =\< 4 x upper limit of normal (ULN)
• Creatinine clearance of \>= 50 mL/min (estimated by the Cockcroft-Gault \[C-G\] formula)
• Male patients must use an effective contraceptive method during the study and for a minimum of 8 weeks after study treatment
• Baseline left ventricular ejection fraction (LVEF) \>= 40%

You may not qualify if:

• Patients with \>= New York Heart Association (NYHA) grade 3 heart disease as assessed by history and/or physical examination
• Patients who received more than one full course of prior hypomethylating agents azacitidine or decitabine
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Pregnant or lactating patients
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
• Any concurrent malignancy with the exception of the following: a) patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; b) patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Interventions

Cladribine; guadecitabine; Idarubicin

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Hagop Kantarjian, MD/Chair
• Organization: The University of Texas MD Anderson Cancer Center

hkantarjian@mdanderson.org

713-792-7026

Study Officials

• Hagop M Kantarjian

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2014
• First Posted: March 26, 2014
• Study Start: April 4, 2014
• Primary Completion: November 24, 2020
• Study Completion: November 24, 2020
• Last Updated: August 27, 2024
• Results First Posted: May 24, 2022

Record last verified: 2024-08

Locations

US (1)