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Guadecitabine in Treating Patients With Higher-Risk Myelodysplastic Syndromes

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ClinicalTrials.gov Identifier: NCT02131597
Recruitment Status : Recruiting
First Posted : May 6, 2014
Last Update Posted : March 25, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well guadecitabine works in treating patients with myelodysplastic syndromes that are at higher risk for becoming acute myeloid leukemia. Guadecitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
High Risk Myelodysplastic Syndrome Drug: Guadecitabine Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the complete response (CR) rate with SGI-110 (guadecitabine) in patients with higher risk myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

I. Overall response rate, survival, transformation to acute myeloid leukemia (AML), transfusion independence.

II. Safety and toxicity.

OUTLINE:

Patients receive guadecitabine subcutaneously (SC) on days 1-5. Treatment repeats every 4-8 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 3 courses are taken off therapy after 6 courses. Patients may continue to receive treatment after 24 courses if the investigator determines it is in the patient's best interest.

After completion of study treatment, patients are followed up at 30 days, and then every 2 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 103 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of SGI-110 in Patients With Higher Risk MDS
Actual Study Start Date : November 10, 2014
Estimated Primary Completion Date : November 1, 2019
Estimated Study Completion Date : November 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (guadecitabine)
Patients receive guadecitabine SC on days 1-5. Treatment repeats every 4-8 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 3 courses are taken off therapy after 6 courses. Patients may continue to receive treatment after 24 courses if the investigator determines it is in the patient's best interest.
Drug: Guadecitabine
Given SC
Other Names:
  • DNMT inhibitor SGI-110
  • S110
  • SGI-110




Primary Outcome Measures :
  1. Complete response rates [ Time Frame: Up to 5 years ]
    Estimated along with 95% credible intervals.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 5 years ]
    The method of Thall, Simon, and Estey will be used to monitor toxicity (adverse events). Summarized using frequency and percentage, by organ type, grade and attribution.

  2. Mortality rate [ Time Frame: At 3 months ]
    The method of Thall, Simon, and Estey will be used to monitor mortality.

  3. Overall response rates [ Time Frame: Up to 5 years ]
    Estimated along with 95% credible intervals.

  4. Overall survival [ Time Frame: Up to 5 years ]
    Estimated using the Kaplan-Meier method for each patient cohort.

  5. Time to acute myeloid leukemia (AML) transformation [ Time Frame: Up to 5 years ]
    Estimated using the Kaplan-Meier method for each patient cohort.

  6. Event-free survival [ Time Frame: Up to 5 years ]
    Estimated using the Kaplan-Meier method for each patient cohort.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with higher risk MDS (International Prognostic Scoring System [IPSS] int-2 or high; or >= 10% blasts as defined by World Health Organization [WHO])

    • No prior intensive chemotherapy or high-dose cytarabine (>= 1 g/m^2)
    • Prior biologic therapies (=< 1 cycle of prior decitabine or azacitidine), targeted therapies, or single agent chemotherapy is allowed
    • Off chemotherapy for 2 weeks prior to entering this study with no toxic effects of that therapy, unless there is evidence of rapidly progressive disease
    • Hydroxyurea is permitted for control of counts prior to treatment
    • Hematopoietic growth factors are allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Serum creatinine =< 1.5 mg/dL
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate transaminase (AST) or alanine transaminase (ALT) =< 2.5 x ULN
  • Alkaline phosphatase =< 2.5 x ULN
  • Provide signed written informed consent
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
  • Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to entering this study
  • Women who are able to become pregnant and men who can father a child must use birth control while on study and for at least 8 weeks after your last dose of study drug(s); acceptable birth control includes a condom or a diaphragm with spermicidal jelly; and birth control methods that are taken by mouth, injected, or implanted; if you are already using birth control, you must check with the study staff to make sure that it is considered one of the acceptable forms to use in this study

Exclusion Criteria:

  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks prior to entering this study with the exception of hydroxyurea; the patient must have recovered from all acute toxicities from any previous therapy
  • 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

    • Exceptions

      • 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
      • 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): NCT02131597


Contacts
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Contact: Guillermo Garcia-Manero 713-745-3428 ggarciam@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Guillermo Garcia-Manero    713-745-3428    ggarciam@mdanderson.org   
Principal Investigator: Guillermo Garcia-Manero         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Guillermo Garcia-Manero M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02131597     History of Changes
Other Study ID Numbers: 2013-0901
NCI-2014-02377 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2013-0901 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: May 6, 2014    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019

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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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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Guadecitabine
Azacitidine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors