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

NCT ID: NCT04526795

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-09

Study Completion Date

2024-11-15

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Cytarabine

Intervention Type DRUG

Given IV

Fludarabine

Intervention Type DRUG

Given IV

Pegcrisantaspase

Intervention Type DRUG

Given IV

Interventions

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Cytarabine

Given IV

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Pegcrisantaspase

Given IV

Intervention Type DRUG

Other Intervention Names

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.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 Fluradosa

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tapan M Kadia

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

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NCI-2020-05459

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-0434

Identifier Type: OTHER

Identifier Source: secondary_id

2020-0434

Identifier Type: -

Identifier Source: org_study_id