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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

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.

Condition or disease Intervention/treatment Phase
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 Drug: Cytarabine Drug: Fludarabine Drug: Pegcrisantaspase Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study of Fludarabine, Cytarabine (Ara-C) and Pegylated Erwinase (Pegcrisantaspase) in Patients With Relapsed or Refractory Leukemia
Estimated Study Start Date : December 31, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
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.

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




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Duration of response [ Time Frame: Up to 20 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04526795


Contacts
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Contact: Tapan M Kadia 713-792-7305 tkadia@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Contact: Tapan M. Kadia    713-792-7305      
Principal Investigator: Tapan M. Kadia         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04526795    
Other Study ID Numbers: 2020-0434
NCI-2020-05459 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0434 ( Other Identifier: M D Anderson Cancer Center )
First Posted: August 26, 2020    Key Record Dates
Last Update Posted: August 26, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Prolymphocytic
Blast Crisis
Leukemia, Biphenotypic, Acute
Leukemia, Prolymphocytic, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Pathologic Processes
Leukemia, T-Cell
Cytarabine
Fludarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action