Clofarabine, Etoposide, and Mitoxantrone for Relapsed and Refractory Acute Leukemias

NCT00882076 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PSHCI 08-096
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to establish toxicity and a maximum tolerated dose recommended phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias. The investigators will observe responses with these therapy agents and assess the impact of Clofarabine interacting with Etoposide in induction of DNA strand breaks.

Conditions

Leukemia

Keywords

acute lymphoblastic leukemia; chronic lymphocytic leukemia

Outcome Measures

Primary Outcomes (3)

• Establish toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias

  Days 30-45

• Establish dose limiting toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias

  Days 30-45

• Establish maximum tolerated dose recommend Phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias

  Days 30-45

Secondary Outcomes (2)

• Observe response of relapsed or refractory acute leukemias to therapy with these agents.

  30-70 days

• Assess the impact of Clofarabine interacting with Etoposide and Mitoxantrone in induction of DNA strand breaks

  30-45 days

Study Arms (5)

Treatment Cohort 1

EXPERIMENTAL

Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (3 doses); Clofarabine (Days 2-6) 20 mg/m2

Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide

Treatment Cohort 2

EXPERIMENTAL

Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 25 mg/m2

Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide

Treatment Cohort 3

EXPERIMENTAL

Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 30 mg/m2

Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide

Treatment Cohort 4

EXPERIMENTAL

Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-5) 8 mg/m2; Clofarabine (Days 2-6) 30 mg/m2

Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide

Treatment Cohort 0

EXPERIMENTAL

Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2; Clofarabine (Days 2-6) 10 mg/m2 (In the event of a DLT in Treatment Cohort 1)

Drug: Clofarabine; Drug: Mitoxantrone; Drug: Etoposide

Interventions

Clofarabine DRUG

For Treatment Clofarabine will be administered on Days 2-6 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Clofarabine will be administered on Days 1-4 at the dose of 20mg/m2 in Cohort 1, 25mg/m2 in Cohort 2 and 30mg/m2 in Cohort 3 and 4 and 10mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1).

Also known as: Clolar

Treatment Cohort 0; Treatment Cohort 1; Treatment Cohort 2; Treatment Cohort 3; Treatment Cohort 4

Mitoxantrone DRUG

For Treatment Mitoxantrone will be administered on Days 1-3 at the dose of 8mg/m2 in Cohort 1, 2, 3 and on Days 1-5 for Cohort 4 and on Days 1-3 8mg/m2 in Cohort 0 (In the event of excessive DLT in Treatment Cohort 1). For Retreatment Mitoxantrone will be administered on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 1, 2 and 3 and on Days 1-4 (4 doses) at the dose of 8mg/m2 in Cohort 4, and on Days 1-2 (2 doses) at the dose of 8mg/m2 in Cohort 0 (In the event of excessive DLT in Retreatment Cohort 1).

Also known as: Mitoxantrone hydrochloride

Treatment Cohort 0; Treatment Cohort 1; Treatment Cohort 2; Treatment Cohort 3; Treatment Cohort 4

Etoposide DRUG

For Treatment Etoposide will be administered on Days 1-5 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Treatment Cohort 1). For Retreatment Etoposide will be administered on Days 1-4 at the dose of 100mg/m2 in Cohort 1, 2, 3, 4 and Cohort 0 (in the event of excessive DLT in Retreatment Cohort 1).

Also known as: Etoposide Phosphate

Treatment Cohort 0; Treatment Cohort 1; Treatment Cohort 2; Treatment Cohort 3; Treatment Cohort 4

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adequate renal and hepatic function.
• Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
• LVEF must be ≥ 50% within 2 weeks.

You may not qualify if:

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment.
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled.
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up or interpretation of study results.
• Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy with the following exceptions: patients with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for the study if definitive treatment for the condition has been completed. Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed. Additionally, patients with prostate cancer treated with radiation therapy are also eligible for the study.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Clofarabine; Mitoxantrone; Etoposide; etoposide phosphate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates

Study Officials

• David F. Claxton, MD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 15, 2009
• First Posted: April 16, 2009
• Study Start: March 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: July 24, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)