Back to results

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

Primary Purpose

Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Recurrent Acute Biphenotypic Leukemia, Recurrent Acute Lymphoblastic Leukemia

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Cytarabine

Fludarabine

Pegcrisantaspase

About this trial

This is an interventional treatment trial for Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

M D Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (pegcrisantaspase, fludarabine, cytarabine)

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)

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

Overall response rate (ORR) of pegcrisantaspase

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

Overall survival (OS)

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)

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

Full Information

NCT ID

NCT04526795

First Posted

August 13, 2020

Last Updated

October 9, 2023

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04526795

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 9, 2021 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment (pegcrisantaspase, fludarabine, cytarabine)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Other Intervention Name(s)

.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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Other Intervention Name(s)

Fluradosa

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Pegcrisantaspase

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Maximum tolerated dose (MTD)

Description

Time Frame

End of cycle 1 (5 weeks)

Secondary Outcome Measure Information:

Title

Overall response rate (ORR) of pegcrisantaspase

Description

Time Frame

Up to 20 weeks

Title

ORR of fludarabine, cytarabine (araC), and pegcrisantaspase

Description

Time Frame

Up to 20 weeks

Title

Overall survival (OS)

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.

Time Frame

From date of treatment start until date of death due to any cause, assessed up to 20 weeks

Title

Disease-free survival (DFS)

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.

Time Frame

From date of remission until the date of first objective documentation ofdisease-relapse or death, assessed up to 20 weeks

Title

Duration of response

Time Frame

Up to 20 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tapan M Kadia

Phone

713-792-7305

tkadia@mdanderson.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tapan M Kadia

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

M D Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tapan M. Kadia

Phone

713-792-7305

First Name & Middle Initial & Last Name & Degree

Tapan M. Kadia

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

MD Anderson Cancer Center

Learn more about this trial

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

We'll reach out to this number within 24 hrs