Phase II Study of Decitabine and Cytarabine for Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

NCT01829503 | Completed Phase 2 Results DMC

• 1 other identifier: 12-099
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: To determine the efficacy of an induction regimen using decitabine as an epigenetic primer followed by cytarabine in the treatment of older patients with newly diagnosed Acute myeloid leukemia (AML). Primary endpoint: Complete remission rates Secondary objective: To determine the safety of an induction regimen of decitabine followed by cytarabine in the treatment of older patients with newly diagnosed AML, evaluate survival and identify potential predictive factors for response to treatment Secondary endpoints:

• Treatment related toxicities
• 4 and 8 week mortality
• Overall survival
• Relapse-free survival
• Predictive factors for response to treatment
• Quality of Life measures including self reported symptoms and assessment of sleep patterns Treatment administration Induction therapy Eligible patients will be treated with induction therapy (decitabine + cytarabine) at the University of Pittsburgh Cancer Center inpatient leukemia service at Shadyside Hospital. Patients will receive decitabine 20mg/m2 in 100mL normal saline (NS) intravenously (IV) over 1 hour daily for five days, followed by cytarabine 100mg/m2 in 1000 mL normal saline (NS) as a continuous IV infusion over 24 hours for 5 days. Treatment should be discontinued or delayed for any of the following during the treatment period: a rise in serum creatinine \> 2x patient baseline or upper limit of normal (whichever is higher) unless there is an identifiable reversible etiology, or ALT, AST or total bilirubin \> 5x upper limit of normal, and should be held until resolution below these parameters. There are no parameters for dose reduction. Patients who have persistent disease on post-treatment bone marrow aspirate and biopsy, will undergo a repeat cycle of induction with decitabine followed by cytarabine as outlined above. Supportive care including blood product transfusions, antiemetic medications antiviral and antifungal medications, or empiric antibiotics may be used at the clinical discretion of the provider. Maintenance therapy Patients in complete response (CR) will proceed to decitabine maintenance therapy, where each treatment will be decitabine 20mg/m2 in 100mL normal saline (NS) intravenously (IV) over 1 hour daily for five days administered in the outpatient setting. Maintenance treatments will be continued until disease relapse. Maintenance treatments can be administered as an outpatient at the Hillman Cancer Center, or at a University of Pittsburgh Medical Center (UPMC) facility that is able to administer chemotherapy under the supervision of an Oncologist Evaluations during maintenance Phase: During maintenance therapy, complete blood count (CBC) w/ diff/platelets, CMP (Na, K, Cl, carbon dioxide (CO2), glucose, blood urea nitrogen (BUN), Cr, Ca, Total Protein, Albumin, AST, ALT, Alk Phos, Total Bilirubin) will be checked each cycle on day 14 \[+/- 4 days\]. Within 7 days of start of new cycle, study visits will include physical exam, adverse events assessment, CBC and comprehensive metabolic panel (CMP). Maintenance cycles will be 28 days \[+/- 7 days\]. Cycles can be held up to 4 weeks \[28 days\]. For start of new cycle, any grade 3 or 4 non-hematologic toxicity possibly, probably or definitely related to decitabine therapy must resolve to grade 2 or baseline. In addition the following lab parameters must be met to start a new cycle of maintenance: Absolute Neutrophil Count (ANC) \> or = 1000/mm3 Platelets \>/= 50,000/mm3 AST or ALT \< 2 x Uppler Limit of Normal (ULN) Total billirubin \< 2 x ULN Serum creatinine \< 2x patient baseline or upper limit of normal (whichever is higher) \[If lab parameters are not met for start of cycle, these labs will be checked a minimum of once per week\]. If start of new cycle is held for more than 4 weeks \[28 days\], the subject will be off treatment. Other reasons for delay in treatment should be discussed with the Principal Investigator.

Conditions

Acute Myeloid Leukemia

Keywords

Phase II; decitabine; cytarabine; older patients; newly diagnosed; AML; Newly Diagnosed AML

Outcome Measures

Primary Outcomes (2)

• Number of Participants by Best Clinical Response Experienced

  The number of participants who experienced either a Complete Response, Complete Response with Incomplete Count Recovery, Partial Response, or Progressive Disease. Complete response: Less than 5% blasts in an aspirate sample of a patient who has an absolute neutrophil count of \>1000µ/L and platelets \>100,000µ/L; Complete response with incomplete count recovery: Complete response except for residual neutropenia (\<1000µ/L) or thrombocytopenia (\<100,000µ/L) Partial response: Decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow aspirate; Progressive disease: Failure to achieve complete response or partial response

  Up to 38 months

• Proportion of Participants With Clinical Response (CR)

  The number of participants (out of 39) who experienced Clinical Response as Complete Response, or, Complete Response + Complete Response with Incomplete Count Recovery (exact Clopper-Pearson confidence interval).

  Up to 38 months

Secondary Outcomes (10)

• Numbers of Patients (Out of 44) Experiencing Adverse Events With CTCAE Grade ≥ 3 or Adverse Events Grade ≥ 4

  Up to 38 months

• Proportion of Participants With Survival to Four and Eight Weeks and One Year

  Up to one year (4 weeks, 8 weeks, and one year)

• Overall Survival (OS)

  Up to 38 months (median follow-up = 25.4 months)

• Overall Survival (OS) in Participants Who Experienced Complete Response

  Up to 38 months (median follow-up = 25.4 months)

• Overall Survival (OS) in Participants Who Experienced Complete Response or Complete Response With Incomplete Count Recovery

  Up to 38 months (median follow-up = 25.4 months)

Study Arms (1)

decitabine and cytarabine

EXPERIMENTAL

Drug: decitabine and cytarabine; Other: Supportive Care

Interventions

decitabine and cytarabine DRUG

decitabine and cytarabine

Supportive Care OTHER

blood product transfusions, antiemetic medications, antiviral and antifungal medications, empiric antibiotics

decitabine and cytarabine

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 70, or age ≥ 60 ineligible for treatment with standard induction chemotherapy (based on physician discretion or patient refusal), with a new diagnosis of AML based on World Health Organization Classification.
• Eastern Cooperative Oncology Group Performance Status of 0-2
• Cardiac ejection fraction ≥45%
• Males are eligible to enter and participate in the study if they have either had a prior vasectomy or agree to avoid sexual activity or use adequate contraception from screening through two months post the last dose of decitabine

You may not qualify if:

• Patients with acute promyelocytic leukemia
• Life expectancy ≤3 months
• Prior use of any hypomethylating agent or cytarabine
• Uncontrolled, life-threatening infection that is not responding to antimicrobial therapy
• Serum creatinine \> 2x upper limit of normal
• Aspartate aminotransferase (AST),alanine aminotransferase (ALT), or total bilirubin \> 5x upper limit of normal
• History of psychiatric disorder which may compromise compliance with the protocol or which does not allow for appropriate informed consent
• Patient may not be receiving any other antineoplastic agents (hydroxyurea is allowed)
• Concurrent malignancy. Exception: Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled.
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease).

Sponsors & Collaborators

• Annie Im, M.D.: lead

Study Sites (1)

University of PIttsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Im A, Quann K, Agha M, Raptis A, Redner RL, Hou JZ, Farah R, Dorritie KA, Sehgal AR, Normolle D, Bovbjerg DH, Aggarwal N, Herman J, Lontos K, Boyiadzis M. Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients. Am J Hematol. 2024 Mar;99(3):380-386. doi: 10.1002/ajh.27212. Epub 2024 Jan 22.

  PMID: 38258329 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; Cytarabine; Palliative Care

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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; Arabinonucleosides; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Results Point of Contact

• Title: Dr. Annie P. Im
• Organization: University of Pittsburgh Cancer Institute

imap@upmc.edu

412-623-2393

Study Officials

• Annie Im, MD

  UPCI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 6, 2013
• First Posted: April 11, 2013
• Study Start: February 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: November 30, 2017
• Last Updated: November 14, 2019
• Results First Posted: September 14, 2017

Record last verified: 2019-11

Locations

US (1)