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Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03586609
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : June 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE July 2, 2018
First Posted Date  ICMJE July 13, 2018
Last Update Posted Date June 7, 2019
Actual Study Start Date  ICMJE October 25, 2018
Estimated Primary Completion Date January 3, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
Rate of complete response (CR/complete response with incomplete recovery [CRi]) [ Time Frame: Up to 5 years ]
The optimum two-stage design will be implemented. Will be estimated along with the 95% confidence intervals.
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
Complete response (CR/complete response with incomplete recovery [CRi]) rate [ Time Frame: Up to 5 years ]
The optimum two-stage design will be implemented. Will be estimated along with the 95% confidence intervals.
Change History Complete list of historical versions of study NCT03586609 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2018)
  • Overall response rate [ Time Frame: Up to 5 years ]
    Will be estimated along with the 95% confidence intervals.
  • Overall survival (OS) [ Time Frame: Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years ]
    Kaplan-Meier method will be used to assess the OS probabilities. The median OS will be reported, along with the 95% confidence intervals.
  • Disease-free survival (DFS) [ Time Frame: Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years ]
    Kaplan-Meier method will be used to assess the DFS probabilities. The median DFS will be reported, along with the 95% confidence intervals.
  • Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]
    The Bayesian approach will be implemented for toxicity monitoring, where toxicity is defined as any grade 3 or higher non-hematological toxicity which is at least possibly related to the treatment that occurs during the first 2 cycles of treatment. Safety data will be summarized by category, severity and frequency.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
  • Overall response rate [ Time Frame: Up to 5 years ]
    Will be estimated along with the 95% confidence intervals.
  • Overall survival (OS) [ Time Frame: Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years ]
    Kaplan-Meier method will be used to assess the OS probabilities. The medina OS will be reported, along with the 95% confidence intervals.
  • Disease-free survival (DFS) [ Time Frame: Time interval between treatment start and the date of death or last follow-up, whichever occurred first, assessed up to 5 years ]
    Kaplan-Meier method will be used to assess the DFS probabilities. The medina DFS will be reported, along with the 95% confidence intervals.
  • Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]
    The Bayesian approach will be implemented for toxicity monitoring, where toxicity is defined as any grade 3 or higher non-hematological toxicity which is at least possibly related to the treatment that occurs during the first 2 cycles of treatment. Safety data will be summarized by category, severity and frequency.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Venetoclax, Cladribine, Low Dose Cytarabine, and Azacitidine in Treating Patients With Previously Untreated Acute Myeloid Leukemia
Official Title  ICMJE Phase II Study of Venetoclax Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Cladribine Plus LDAC Alternating With 5-Azacitidine With Venetoclax in Patients With Untreated AML
Brief Summary This phase II trial studies how well venetoclax, cladribine, low dose cytarabine, and azacitidine work in treating patients with acute myeloid leukemia that has previously not been treated. Drugs used in chemotherapy, such as venetoclax, cladribine, and low dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax, cladribine, low dose cytarabine induction followed by cladribine, low dose cytarabine, and azacitidine consolidation may work better in treating patients with acute myeloid leukemia.
Detailed Description

PRIMARY OBJECTIVES:

I. To assess the complete response (CR/complete response with incomplete recovery [CRi]) rate of patients with acute myeloid leukemia (AML) treated with venetoclax combined with cladribine (2-CDA) plus low-dose cytarabine (LDAC) alternating with 5-azacytidine (AZA).

SECONDARY OBJECTIVES:

I. To assess overall survival (OS) of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.

II. To assess the disease free survival (DFS) patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine and achieved a complete response (CR/CRi).

III. To assess the overall response rate of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.

IV. To assess toxicity and induction mortality of patients with AML treated with venetoclax added to cladribine plus LDAC alternating with 5-azacytidine.

OUTLINE:

INDUCTION: Patients receive cladribine intravenously (IV) daily over 1-2 hours on days 1-5, cytarabine subcutaneously (SC) twice daily (BID) on days 1-10, and venetoclax orally (PO) daily on days 1-21. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after course 1 may receive a second induction cycle. Patients who do not achieve CR or CRi after second induction cycle may proceed to cycle 3 of consolidation per investigator.

CONSOLIDATION/MAINTENANCE:

Patients who achieve CR or CRi after cycle 1 of induction receive cladribine IV over 1-2 hours daily on days 1-3, cytarabine SC BID on days 1-10, and venetoclax PO once daily (QD) on days 1-21 of cycle 2. All patients receive cladribine IV daily over 1-2 hours of cycles 5-6, 9-10, 13-14, and 17-18, cytarabine SC BID on days 1-3 of cycles 5-6, 9-10, 13-14, and 17-18, venetoclax PO QD on days 1-21 of cycle 3-18, and azacitidine SC daily or IV over 30-60 minutes on days 1-7 of cycles 3-4, 7-8, 1-12, and 15-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months for 5 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Azacitidine
    Given SC or IV
    Other Names:
    • 5 AZC
    • 5-AC
    • 5-Azacytidine
    • 5-AZC
    • Azacytidine
    • Azacytidine, 5-
    • Ladakamycin
    • Mylosar
    • U-18496
    • Vidaza
  • Drug: Cladribine
    Given IV
    Other Names:
    • 2-CdA
    • 2CDA
    • CdA
    • Cladribina
    • Leustat
    • Leustatin
    • Leustatine
    • RWJ-26251
  • Drug: Cytarabine
    Given SC
    Other Names:
    • .beta.-Cytosine arabinoside
    • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-.beta.-D-Arabinofuranosylcytosine
    • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-Beta-D-arabinofuranosylcytosine
    • 1.beta.-D-Arabinofuranosylcytosine
    • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
    • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
    • Alexan
    • Ara-C
    • ARA-cell
    • Arabine
    • Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Aracytidine
    • Aracytin
    • Aracytine
    • Beta-cytosine Arabinoside
    • CHX-3311
    • Cytarabinum
    • Cytarbel
    • Cytosar
    • Cytosine Arabinoside
    • Cytosine-.beta.-arabinoside
    • Cytosine-beta-arabinoside
    • Erpalfa
    • Starasid
    • Tarabine PFS
    • U 19920
    • U-19920
    • Udicil
    • WR-28453
  • Drug: Venetoclax
    Given PO
    Other Names:
    • ABT-0199
    • ABT-199
    • ABT199
    • GDC-0199
    • RG7601
    • Venclexta
    • Venclyxto
Study Arms  ICMJE Experimental: Treatment (cladribine, cytarabine, venetoclax, azacitidine)
See Detailed Description.
Interventions:
  • Drug: Azacitidine
  • Drug: Cladribine
  • Drug: Cytarabine
  • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2018)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 3, 2021
Estimated Primary Completion Date January 3, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with previously untreated acute myeloid leukemia (AML). Prior therapy with hydroxyurea, hematopoietic growth factors, HMA, all-trans retinoic acid (ATRA), or a total dose of cytarabine up to 2 g (for emergency use for stabilization) is allowed.
  • Patients aged < 60 years who are unsuitable for standard induction therapy may be eligible after discussion with primary investigator.
  • Bilirubin =< 2 mg/dL. Unless liver enzyme abnormalities are determined by the treating Doctor of Medicine (MD) and principal investigator (PI) to be due to leukemic infiltration.
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (AL)T =< 3 x ULN. Unless liver enzyme abnormalities are determined by the treating MD and PI to be due to leukemic infiltration.
  • Creatinine =< 1.5 x upper limit of normal (ULN).
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2.
  • A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
  • Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol.

Exclusion Criteria:

  • Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patient with documented hypersensitivity to any of the components of the chemotherapy program.
  • Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.
  • Prior therapy with venetoclax.
  • Patients with a diagnosis of acute promyelocytic leukemia (AML-M3) will be excluded from this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tapan Kadia 713-563-3534 kadia@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03586609
Other Study ID Numbers  ICMJE 2018-0020
NCI-2018-01318 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0020 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP