Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory AML and MDS

NCT01607645 | Terminated Phase 2 Results

• 3 other identifiers: 2588.00NCI-2012-00769P30CA015704
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this study are to learn about the effectiveness, the side-effects, if waiting to give the idarubicin and cytarabine may change the side effects or effectiveness, and to identify factors to predict for responses to this therapy. The trial will examine combination of three chemotherapy drugs. These drugs are decitabine, idarubicin, and cytarabine.

Conditions

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved Morphologic CR

  Morphologic complete remission (CR): Absolute Neutrophil Count (ANC)≥1,000/uL, platelet count ≥100,000/uL, \<5% Bone Marrow (BM) blasts, no Auer rods (cytoplasmic inclusions which result from an abnormal fusion of the primary (azurophilic) granules), no morphologic dysplasia, and no evidence of extramedullary disease

  Participants were monitored up until the point when they went off study following completion of the treatment (3 months)

Secondary Outcomes (12)

• Resistant Disease Defined as Patient Survives at Least 14 Days After Completion of the Last Dose of Induction or Re-induction But Has Persistent Leukemia in Peripheral Blood (PB) or BM

  Assessed for up to 90 days

• Cytogenetic Response Defined as no Detectable Cytogenetic Abnormality in a Subsequent BM Specimen After Induction or Re-induction

  Assessed for up to 5 years

• CRMRD- Defined as Morphologic CR Without Evidence of Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers

  Assessed for up to 5 years

• CRi Defined as Meeting All Criteria for a Morphologic CR But ANC Remains Less Than 1,000/μL and/or Platelet Count Less Than 100,000/μL

  Assessed for up to 5 years

• CRMRD+ Defined as a Morphologic CR But With Minimal Residual Disease by Flow Cytometry, Cytogenetics, or Other Known Molecular Biomarkers

  Assessed for up to 5 years

Study Arms (2)

Arm1: decitabine, idarubicin, cytarabine

EXPERIMENTAL

Patients receive decitabine IV over 1 hour on days -4 to 0, cytarabine IV continuously over 24 hours on days 1-7, and idarubicin IV over 10-15 minutes on days 1-3.

Drug: decitabine; Drug: idarubicin; Drug: cytarabine

Arm2: decitabine, idarubicin, cytarabine

EXPERIMENTAL

Patients receive decitabine IV over 1 hour on days -9 to -5 and cytarabine and idarubicin as in Arm I.

Drug: decitabine; Drug: idarubicin; Drug: cytarabine

Interventions

decitabine DRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC

Arm1: decitabine, idarubicin, cytarabine; Arm2: decitabine, idarubicin, cytarabine

idarubicin DRUG

Given IV

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

Arm1: decitabine, idarubicin, cytarabine; Arm2: decitabine, idarubicin, cytarabine

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm1: decitabine, idarubicin, cytarabine; Arm2: decitabine, idarubicin, cytarabine

Eligibility Criteria

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

You may qualify if:

• Written informed consent
• All patients except those with acute promyelocytic leukemia (APL) who have morphological diagnosis of myelodysplastic syndromes (MDS) refractory anemia with excess blasts (RAEB)-II or AML by World Health Organization (WHO) diagnostic criteria and have either refractory or early relapsed disease; NOTE:
• Diagnosis of refractory or relapsed disease must be based on evaluation of a bone marrow (BM) aspirate or peripheral blood (PB) flow cytometry; other standard MDS and AML prognostic studies such as cytogenetics, flow, and molecular testing are highly recommended prior to initiating DAC
• A previous BM evaluation or PB flow cytometry from an outside facility are acceptable if the results have been deemed to be adequate for confirming the diagnosis and staging by University of Washington (UW)/Seattle Cancer Care Alliance (SSCA)/Fred Hutchinson Cancer Research Center (FHCRC) review
• A BM biopsy is not routinely required but should be obtained if the previous evaluation is not deemed to be adequate for confirming diagnosis and staging by UW/SCCA/FHCRC review
• Must have received at least one previous cycle of treatment for myelodysplastic syndrome (MDS) or AML and be either refractory as defined as not responded to this therapy or in early relapse as defined as developing recurrence of the disease within 12 months of obtaining a CR
• May have previously received demethylating agents (e.g., DAC, 5-azacytidine \[5AZA\]) or histone deacetylases (e.g., suberoylanilide hydroxamic acid) for their MDS or AML if these demethylating agents were not used in combination with systemic anthracycline and ARAC chemotherapy
• May have received hematopoietic growth factors, thalidomide/lenalidomide, signal transduction inhibitors, or low dose cytarabine (=\< 20 mg/m2/day)
• May not have received any therapy for their MDS or AML other than hydroxyurea or leukapheresis for at least 14 days prior to start of the first dose of DAC; all non-hematologic toxicities must have resolved to \< grade 2
• Must have a "simplified" treatment-related mortality (TRM) score =\< 9.2
• Females of childbearing potential must have a negative pregnancy test prior to initiation of the protocol therapy; females are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 12 weeks after treatment discontinuation
• Patients with an active or history of other malignancies are eligible, if their projected overall survival for that malignancy is at least 6 months
• Prior hormonal therapy such as aromatase inhibitors, selective estrogen receptor modulators, estrogen receptor down-regulators, luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, and anti-androgens, must be completed at least 30 days prior to initiation of protocol therapy and must remain off hormonal therapy until the patient has finished chemotherapy for their MDS-RAEBII or AML
• Direct bilirubin =\< 2.5 mg/dL (assessed within 14 days prior to registration) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis

You may not qualify if:

• Previous therapy with demethylating agents (e.g., DAC, 5AZA, etc.) or histone deacetylases (e.g., suberoylanilide hydroxamic acid, etc.) that was combined with daunorubicin (DNR) or IDA and ARAC
• Patients with acute promyelocytic leukemia (APL)
• Known hypersensitivity to DAC, ARAC, or IDA
• Clinical evidence of CNS involvement with leukemia, unless a lumbar puncture confirms the absence of leukemic blasts in the CSF
• Prior positive test for HIV
• Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• A "simplified" TRM score \> 9.2
• Bilirubin \> 2.5 mg/dl (assessed within 14 days prior to registration), unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
• Patients who have a projected overall survival \< 6 months due to malignancies other than MDS or AML
• Documented symptomatic congestive heart failure or a documented left ventricular ejection fraction \< 40% assessed by multigated acquisition (MUGA), echocardiography, or heart catheterization within 21 days prior to start of decitabine

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

Decitabine; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Arabinonucleosides

Limitations and Caveats

Early termination due to similar competing protocol, which made statistical evaluation of primary endpoint and any meaningful evaluation of secondary time points not feasible.

Results Point of Contact

• Title: Derek L. Stirewalt
• Organization: FHCRC

dstirewa@fhcrc.org

2066675386

Study Officials

• Derek Stirewalt

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 25, 2012
• First Posted: May 30, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 31, 2017
• Results First Posted: March 31, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)