Clinical Trials /

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

NCT04526795

Description:

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.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Leukemia
  • T-Cell Prolymphocytic Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Fludarabine, Cytarabine, and Pegcrisantaspase for the Treament of Relapsed or Refractory Leukemia
  • Official Title: Phase Ib Study of Fludarabine, Cytarabine (Ara-C) and Pegylated Erwinase (Pegcrisantaspase) in Patients With Relapsed or Refractory Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 2020-0434
  • SECONDARY ID: NCI-2020-05459
  • SECONDARY ID: 2020-0434
  • NCT ID: NCT04526795

Conditions

  • 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

Interventions

DrugSynonymsArms
Cytarabine.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-28453Treatment (pegcrisantaspase, fludarabine, cytarabine)
FludarabineFluradosaTreatment (pegcrisantaspase, fludarabine, cytarabine)
PegcrisantaspaseTreatment (pegcrisantaspase, fludarabine, cytarabine)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pegcrisantaspase, fludarabine, cytarabine)ExperimentalINDUCTION: 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.
  • Cytarabine
  • Fludarabine
  • Pegcrisantaspase

Eligibility Criteria

        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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD)
Time Frame:End of cycle 1 (5 weeks)
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Overall response rate (ORR) of pegcrisantaspase
Time Frame:Up to 20 weeks
Safety Issue:
Description: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.
Measure:ORR of fludarabine, cytarabine (araC), and pegcrisantaspase
Time Frame:Up to 20 weeks
Safety Issue:
Description: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.
Measure:Overall survival (OS)
Time Frame:From date of treatment start until date of death due to any cause, assessed up to 20 weeks
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Duration of response
Time Frame:Up to 20 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 24, 2020