Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome

NCT01165996 | Completed Phase 1 Results DMC

• 2 other identifiers: CASE2908NCI-2010-00135
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Thrombocytopenia

Keywords

previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of Patients That Experience > Grade 2 Non-hematologic Toxicity by National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) v4 Criteria

  up to 12 months of treatment

• Cytogenetic Response as Per IWG Criteria

  at 12 months

• Proportion of Patients With Pharmacodynamic Evidence of Drug Effect.

  6 weeks after treatment

• Proportion of Patients With Bone Marrow Evidence of Cytotoxicity.

  6 weeks after treatment

• Proportion of Patients With Bone Marrow Evidence of Terminal Differentiation Response to Therapy.

  6 weeks after treatment

Study Arms (1)

Arm I: decitabine

EXPERIMENTAL

INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts \< 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

Other: flow cytometry; Other: DNA methylation analysis; Other: cytogenetic analysis; Drug: decitabine; Genetic: microarray analysis; Genetic: gene expression analysis; Other: pharmacological study; Genetic: polymorphism analysis

Interventions

flow cytometry OTHER

Correlative studies

Arm I: decitabine

DNA methylation analysis OTHER

Correlative studies

Arm I: decitabine

cytogenetic analysis OTHER

Correlative studies

Arm I: decitabine

decitabine DRUG

Given subcutaneously

Also known as: 5-aza-dCyd, 5AZA, DAC, Dacogen, deoxyazacytidine, dezocitidine

Arm I: decitabine

microarray analysis GENETIC

Correlative studies

Also known as: gene expression profiling

Arm I: decitabine

gene expression analysis GENETIC

Correlative studies

Arm I: decitabine

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I: decitabine

polymorphism analysis GENETIC

Correlative studies

Arm I: decitabine

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

Related Publications (2)

• 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. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.

  PMID: 16609072 BACKGROUND

• Saunthararajah Y, Sekeres M, Advani A, Mahfouz R, Durkin L, Radivoyevitch T, Englehaupt R, Juersivich J, Cooper K, Husseinzadeh H, Przychodzen B, Rump M, Hobson S, Earl M, Sobecks R, Dean R, Reu F, Tiu R, Hamilton B, Copelan E, Lichtin A, Hsi E, Kalaycio M, Maciejewski J. Evaluation of noncytotoxic DNMT1-depleting therapy in patients with myelodysplastic syndromes. J Clin Invest. 2015 Mar 2;125(3):1043-55. doi: 10.1172/JCI78789. Epub 2015 Jan 26.

  PMID: 25621498 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Thrombocytopenia

Interventions

Flow Cytometry; DNA Methylation; Cytogenetic Analysis; Decitabine; Microarray Analysis; Gene Expression Profiling; Amplified Fragment Length Polymorphism Analysis

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Genetic Techniques; Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Microchip Analytical Procedures; DNA Fingerprinting; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques

Results Point of Contact

• Title: Yogen Saunthararajah, MD
• Organization: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

saunthy@ccf.org

216-444-8170

Study Officials

• Yogen Saunthararajah

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Brenda Cooper, MD

  Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2010
• First Posted: July 20, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2011
• Study Completion: August 1, 2012
• Last Updated: March 4, 2019
• Results First Posted: February 26, 2013

Record last verified: 2019-02

Locations

US (2)