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Fludarabine, Cytarabine, and Pegcrisantaspase for the Treament of Relapsed or Refractory Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04526795
Recruitment Status : Not yet recruiting
First Posted : August 26, 2020
Last Update Posted : August 26, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 13, 2020
First Posted Date  ICMJE August 26, 2020
Last Update Posted Date August 26, 2020
Estimated Study Start Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2020)
Maximum tolerated dose (MTD) [ Time Frame: End of cycle 1 (5 weeks) ]
Measured by dose limiting toxicities (DLTs). DLTs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5) by organ system. DLT will be defined as drug-related adverse events during cycle one (during the lead-in phase).
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2020)
  • Overall response rate (ORR) of pegcrisantaspase [ Time Frame: Up to 20 weeks ]
    The overall response rate for each cohort will be calculated and confidence interval will be provided. Chi square test or Fisher's exact test will be used to evaluate the association between patient prognostic factor and response.
  • ORR of fludarabine, cytarabine (araC), and pegcrisantaspase [ Time Frame: Up to 20 weeks ]
    The overall response rate for each cohort will be calculated and confidence interval will be provided. Chi square test or Fisher's exact test will be used to evaluate the association between patient prognostic factor and response.
  • Overall survival (OS) [ Time Frame: From date of treatment start until date of death due to any cause, assessed up to 20 weeks ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
  • Disease-free survival (DFS) [ Time Frame: From date of remission until the date of first objective documentation ofdisease-relapse or death, assessed up to 20 weeks ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
  • Duration of response [ Time Frame: Up to 20 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fludarabine, Cytarabine, and Pegcrisantaspase for the Treament of Relapsed or Refractory Leukemia
Official Title  ICMJE Phase Ib Study of Fludarabine, Cytarabine (Ara-C) and Pegylated Erwinase (Pegcrisantaspase) in Patients With Relapsed or Refractory Leukemia
Brief Summary This phase Ib trial investigates the side effects and best dose of pegcrisantaspase when given together with fludarabine and cytarabine for the treatment of patients with leukemia that has come back (relapsed) or has not responded to treatment (refractory). Pegcrisantaspase may block the growth of cancer cells. Chemotherapy drugs, such as fludarabine and 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. Giving pegcrisantaspase in combination with fludarabine and cytarabine may work better in treating patients with leukemia compared to the combination of fludarabine and cytarabine.
Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of fludarabine, cytarabine (araC), and pegcrisantaspase in patients with relapsed and refractory leukemias.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (complete remission [CR], CR with incomplete count recovery [CRi], partial remission [PR], or morphologic leukemia free state [MLFS]) of a lead-in dose of single-agent pegcrisantaspase in patients with relapsed and refractory leukemias.

II. To determine the overall response rate (complete remission [CR], CR with incomplete count recovery [CRi], partial remission [PR], or morphologic leukemia free state [MLFS]) of fludarabine, araC, and pegcrisantaspase in patients with relapsed and refractory leukemias.

III. To assess overall survival (OS) and disease-free survival (DFS) of patients treated with fludarabine, araC, and pegcrisantaspase.

IV. To assess the duration of response to the combination in patients with advanced leukemias.

V. To characterize the pharmacokinetics (PK) pharmacodynamics (PD) anti-drug antibodies (ADA) of pegcrisantaspase in patients with relapsed and refractory leukemias.

EXPLORATORY OBJECTIVE:

I. Explore pretreatment and on-treatment biological correlates to predict sensitivity/resistance of pegcrisantaspase-based therapy.

OUTLINE: This is a dose-escalation study of pegcrisantaspase.

INDUCTION: Patients receive pegcrisantaspase intravenously (IV) over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-11 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-10. Treatment repeats every 5 weeks for up 3 cycles in the absence of disease progression or unacceptable toxicity.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Recurrent Acute Biphenotypic Leukemia
  • Recurrent Acute Lymphoblastic Leukemia
  • Recurrent Acute Myeloid Leukemia
  • Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Recurrent T-Cell Prolymphocytic Leukemia
  • Refractory Acute Biphenotypic Leukemia
  • Refractory Acute Lymphoblastic Leukemia
  • Refractory Acute Myeloid Leukemia
  • Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Refractory T-Cell Prolymphocytic Leukemia
Intervention  ICMJE
  • Drug: Cytarabine
    Given IV
    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: Fludarabine
    Given IV
    Other Name: Fluradosa
  • Drug: Pegcrisantaspase
    Given IV
Study Arms  ICMJE Experimental: Treatment (pegcrisantaspase, fludarabine, cytarabine)

INDUCTION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-11 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive pegcrisantaspase IV over 60 minutes on days 1 and 15, and fludarabine IV over 15-30 minutes and cytarabine IV over 2 hours on days 8-10. Treatment repeats every 5 weeks for up 3 cycles in the absence of disease progression or unacceptable toxicity.

Interventions:
  • Drug: Cytarabine
  • Drug: Fludarabine
  • Drug: Pegcrisantaspase
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 24, 2020)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with a diagnosis of relapsed or refractory leukemia including, but not limited to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), T-cell prolymphocytic leukemia, biphenotypic acute leukemia, or blast-phase of chronic myeloid Leukemia (CML) will be allowed during the safety lead-in phase
  • For cohort A of the expansion phase: Patients with a diagnosis untreated adverse-risk AML (as defined by ELN [European Leukemia Net Classification] 2017) will be enrolled
  • For cohort B of the expansion phase: Patients with a diagnosis of relapsed or refractory AML will be enrolled
  • Bilirubin =< 2 mg/dL
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Creatinine =< 1.5 x ULN
  • Cardiac ejection fraction of > or = 45% within the past 3 months
  • Amylase and lipase =< 1.5 x ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • A negative urine pregnancy test is required within one week (7 days) for all women of childbearing potential prior to being registered 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 active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, clinically significant 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
  • Prior treatment with pegylated asparaginase
  • Patients with a diagnoses of acute promyelocytic leukemia (AML-M3) will be excluded from this trial
  • 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. Effective methods of birth control include:

    • Birth control pills, shots, implants or patches
    • Intrauterine devices (IUDs)
    • Condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide
    • Abstinence
    • Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy
  • Patients with history of clinically significant venous thromboembolism
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tapan M Kadia 713-792-7305 tkadia@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04526795
Other Study ID Numbers  ICMJE 2020-0434
NCI-2020-05459 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0434 ( Other Identifier: M D Anderson Cancer Center )
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 August 2020

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