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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02096055
Recruitment Status : Active, not recruiting
First Posted : March 26, 2014
Last Update Posted : June 22, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Untreated Adult Acute Myeloid Leukemia Drug: Cladribine Drug: Guadecitabine Drug: Idarubicin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Four-Arm Randomized Phase II Study of SGI-110: 5 Days, Versus 10 Days, Versus 5 Days + Idarubicin, Versus 5 Days + Cladribine, in Previously Untreated Patients >/= 70 Years With Acute Myeloid Leukemia
Actual Study Start Date : April 4, 2014
Estimated Primary Completion Date : April 30, 2026
Estimated Study Completion Date : April 30, 2027


Arm Intervention/treatment
Experimental: Arm I (guadecitabine)

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
Given SC
Other Names:
  • DNMT inhibitor SGI-110
  • S110
  • SGI-110

Experimental: Arm II (CLOSED) (guadecitabine)

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
Given SC
Other Names:
  • DNMT inhibitor SGI-110
  • S110
  • SGI-110

Experimental: Arm III (guadecitabine, idarubicin)

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
Given SC
Other Names:
  • DNMT inhibitor SGI-110
  • S110
  • SGI-110

Drug: Idarubicin
Given IV
Other Names:
  • 4-Demethoxydaunomycin
  • 4-demethoxydaunorubicin
  • 4-DMDR

Experimental: Arm IV (CLOSED) (guadecitabine, cladribine)

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
Given IV
Other Names:
  • 2-CdA
  • 2CDA
  • CdA
  • Cladribina
  • Leustat
  • Leustatin
  • Leustatine
  • RWJ-26251

Drug: Guadecitabine
Given SC
Other Names:
  • DNMT inhibitor SGI-110
  • S110
  • SGI-110




Primary Outcome Measures :
  1. Complete remission rate [ Time Frame: Up to 12 years ]
    Complete remission rates will be presented with 95% confidence intervals. The association between complete remission rates and patient and clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.

  2. Remission duration [ Time Frame: Up to 12 years ]
    Characteristics of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range. The two-sided log-rank test will be used to assess the differences of time to events between groups.

  3. Leukemia-free survival [ Time Frame: Up to 12 years ]
    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.

  4. Survival [ Time Frame: Up to 12 years ]
    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.

  5. Incidence of toxicities [ Time Frame: Up to 12 years ]
    Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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%

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02096055


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Hagop M Kantarjian M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02096055    
Other Study ID Numbers: 2013-0843
NCI-2014-00981 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2013-0843 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2014    Key Record Dates
Last Update Posted: June 22, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Idarubicin
Cladribine
2-chloro-3'-deoxyadenosine
Guadecitabine
Azacitidine
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites