Phase II Study of Fludarabine, Cytarabine (ARA-C) and Erwinase IV in Patients With Relapsed or Refractory Hematologic Malignancies

NCT02718755 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 2015-0807NCI-2016-00691
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical research study is to learn if fludarabine, cytarabine (ARA-C), and erwinase (also known as asparaginase \[erwinia\]) in combination can help to control relapsed or refractory hematologic malignancies. The safety of these drugs will also be studied.

Conditions

Hematologic Malignancy

Keywords

Hematologic malignancy; Relapsed and refractory hematologic malignancies; Acute myeloid leukemia; AML; Acute lymphoblastic leukemia; ALL; Burkitt's leukemia/lymphoma; Prolymphocytic leukemia; Biphenotypic acute leukemia; Blast-phase of chronic myeloid leukemia; CML; B-cell lymphoma; Richter's transformation of chronic lymphocytic leukemia; CLL; Fludarabine; Fludarabine phosphate; Fludara; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine arabinosine hydrochloride

Outcome Measures

Primary Outcomes (1)

• Overall Response of Fludarabine, Cytarabine, and Erwinase in Refractory/Relapsed Hematologic Malignancies

  Response assessed according to the Revised Recommendations of the International Working Group Response Criteria in Acute Myeloid Leukemia.

  56 days

Secondary Outcomes (1)

• Disease-Free Survival (DFS) of Fludarabine, Cytarabine, and Erwinase in Refractory/Relapsed Hematologic Malignancies

  21 days

Study Arms (1)

Fludarabine + Cytarabine + Erwinase

EXPERIMENTAL

Induction Phase: Participants receive 1-2 cycles during the Induction phase. Participants receive 1-2 cycles during the Induction phase. Participants receive Fludarabine by vein on Days 1-5 and Cytarabine by vein. Participants receive Erwinase by vein or as an injection into the muscle on Days 1-7. Consolidation Phase: Participants receive up to 3 cycles during the Consolidation phase. Participants receive Fludarabine by vein on Days 1-4 and Cytarabine by vein. On Day 1 and then every other day for 15 days (3, 5, 7 and so on), participant receives Erwinase by vein or as an injection into the muscle.

Drug: Fludarabine; Drug: Cytarabine; Drug: Erwinase

Interventions

Fludarabine DRUG

Induction Phase: 30 mg/m2 by vein over 15-30 minutes on Days 1 - 5 of a 28 day cycle. Consolidation Phase: 30 mg/m2 by vein over 15-30 minutes on Days 1 - 4 of a 28 day cycle.

Also known as: Fludarabine Phosphate, Fludara

Fludarabine + Cytarabine + Erwinase

Cytarabine DRUG

Induction Phase: 2 grams/m2 by vein over approximately 2 hours on Days 1 - 5 of a 28 day cycle. Consolidation Phase: 2 grams/m2 by vein over approximately 2 hours on Days 1 - 4 of a 28 day cycle.

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Fludarabine + Cytarabine + Erwinase

Erwinase DRUG

Induction Phase: 25,000 Units/m2 by vein (or intramuscularly) over 90-120 minutes on Days 1 - 7 of a 28 day cycle. Consolidation Phase: 25,000 Units/m2 by vein (or intramuscularly) over 90-120 minutes every other day on Days 1, 3, 5, 7, 9, 11, 13, 15 of a 28 day cycle.

Also known as: L-asparaginase, Erwinia L-Asparaginase, Erwinia Chrysanthemi L-asparaginase

Fludarabine + Cytarabine + Erwinase

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with a diagnosis of relapsed or refractory hematologic malignancy including, but not limited to Acute myeloid leukemia (AML), Acute lymphoblastic leukemia (ALL), Burkitt's leukemia/lymphoma, Prolymphocytic leukemia, Biphenotypic acute leukemia, Blast-phase of chronic myeloid leukemia (CML), B-cell lymphoma, or Richter's transformation of chronic lymphocytic leukemia (CLL)
• Age \</= 60 years.
• Adequate organ function as defined below: liver function (bilirubin \< 2mg/dL, AST and/or ALT \<2.5 x upper limits of normal (ULN)), kidney function (creatinine \< 1.5 x ULN ), known cardiac ejection fraction of \> or = 45% within the past 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2.
• \) A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling 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.
• \) 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.

You may not qualify if:

• 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 (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.
• 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.
• Patients with history of clinically significant venous thromboembolism.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Jazz Pharmaceuticals: collaborator

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Hematologic Neoplasms; Recurrence; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Lymphoma; Leukemia, Prolymphocytic; Leukemia, Biphenotypic, Acute; Lymphoma, B-Cell

Interventions

fludarabine; fludarabine phosphate; Cytarabine; Asparaginase; asparaginase erwinia chrysanthemi recombinant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Tapan Kadia, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 24, 2016
• Study Start: May 1, 2018
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2022
• Last Updated: June 26, 2018

Record last verified: 2018-06