Myelodysplastic Syndromes Clinical Trial
Official title:
A Proof of Concept Study of Non-DNA Damaging DNMT1 Depletion Therapy for Myelodysplastic Syndrome
Verified date | February 2019 |
Source | Case Comprehensive Cancer Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
RATIONALE: Decitabine may help myelodysplastic cells become more like normal stem cells. PURPOSE: This clinical trial studies differentiation therapy with decitabine in treating patients with myelodysplastic syndrome.
Status | Completed |
Enrollment | 25 |
Est. completion date | August 2012 |
Est. primary completion date | December 2011 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion - MDS classified by hematopathology review as WHO categories refractory anemia (RA) or refractory cytopenia with multi-lineage dysplasia (RCMD) or refractory anemia with ring sideroblasts (RARS) or refractory anemia with excess blasts (RAEB1 or RAEB2) or chronic myelo-monocytic leukemia (CMML1 or CMML2) - Symptomatic anemia OR thrombocytopenia with a platelet count of < 100 x 10^9/L OR transfusion dependence for red-cells OR transfusion dependence for platelets OR absolute neutrophil count < 1 x 10^9/L Exclusion - MDS of the WHO sub-types RA or RCMD with sole 5q- abnormality on cytogenetics unless failed lenalidomide (Revlimid) therapy - Previous treatment with decitabine - Untreated erythropoietin deficiency defined as an erythropoietin level of < 200 IU/L and erythropoietin replacement therapy for < 8 weeks (erythropoietin deficiency until corrected) - Uncontrolled infection - Severe sepsis or septic shock - Current pregnancy or breast feeding - The patient is of childbearing age, and is unwilling to use contraception and has not had a tubal ligation, hysterectomy, or vasectomy , or their partner is also unwilling to use an acceptable method of contraception as determined by the investigator - Not able to give informed consent - Altered mental status or seizure disorder - ALT > 300 IU; or albumin < 2.0 mg/dL - Creatinine > 2.5 mg/dl and creatinine clearance < 60ml/min - B12, folate, or iron deficient, until corrected - NYHA class III/IV status - ECOG performance status > 2 - HIV positive or history of seropositivity for HIV - Transformation to acute leukemia ( >= 20% myelo-blasts in marrow aspirate) - Any experimental agents other than the study drug decitabine |
Country | Name | City | State |
---|---|---|---|
United States | Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland | Ohio |
United States | Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland | Ohio |
Lead Sponsor | Collaborator |
---|---|
Case Comprehensive Cancer Center |
United States,
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. Epub 2006 Apr 11. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia | Complete Response (CR) include less than 5% marrow blasts without evidence of dysplasia and normalization of peripheral blood counts, including a hemoglobin level of 110 g/L or more, a neutrophil count of 1.5 × 109/L or more, and a platelet count of 100 × 109/L or more. For PR, patients must demonstrate all CR criteria if abnormal before treatment except that marrow blasts should decrease by 50% or more compared with pretreatment levels, or patients may demonstrate a less-advanced MDS disease category than prior to treatment. Stable disease (SD) is defined by failure to achieve at least a partial response but no evidence of progression. Disease progression (DP) includes at least 50% decrease from maximum remission in granulocytes or platelets, reduction in hemoglobin by greater than or equal to 2g/dL, or transfusion dependence. Hematologic improvement (HI) includes hemoglobin increase by at least 1.5g/dL, reduction in transfusions, increase of platelets, increase of neutrophil count | Formal assessment at week 12 for study primary end-point (hematologic improvement). | |
Secondary | Number of Patients That Experience > Grade 2 Non-hematologic Toxicity by National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) v4 Criteria | Incidence of treatment-emergent adverse events (AEs) will be presented in tables that include causality, seriousness, severity/grade, and whether the AE resulted in death or discontinuation of treatment, Laboratory data will be summarized in tables that show changes from pre-treatment values and frequencies of abnormal values. Descriptive statistics will also be provided. | up to 12 months of treatment | |
Secondary | Cytogenetic Response as Per IWG Criteria | Described as the number of patients with a major cytogenetic response (refers to disappearance of a cytogenetic abnormality) or a minor cytogenetic response (50% or more reduction of abnormal metaphases). | at 12 months | |
Secondary | Proportion of Patients With Pharmacodynamic Evidence of Drug Effect. | Evidence of pharmacodynamic effect will be correlated with clinical response criteria. The pharmacodynamic effect of treatment is defined as the number of participants that had depletion DNMT1 with minimal DNA damage and cytotoxicity. | 6 weeks after treatment | |
Secondary | Proportion of Patients With Bone Marrow Evidence of Cytotoxicity. | Cytotoxicity is the ability to destroy cells. This will be measured by taking bone marrow samples and measuring the damage to cells. The level of cell destruction will be correlated with clinical response criteria. | 6 weeks after treatment | |
Secondary | Proportion of Patients With Bone Marrow Evidence of Terminal Differentiation Response to Therapy. | Number of participants who, after therapy, had more of the differentiated types of blood (red cells, platelets, and white cells) compared to abnormal bone marrow cells than before therapy | 6 weeks after treatment | |
Secondary | Proportion of Patients With Particular Genetic Abnormalities Detected by Whole Exome Sequencing Correlation With Clinical Response | Proportion of patients with particular genetic abnormalities, including DNA Methyltransferase 1 (DNMT1) depletion, detected by whole exome sequencing correlation with clinical response | Baseline |
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