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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
David F. Claxton, MD, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00882076
First received: April 15, 2009
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Etoposide, Mitoxantrone, Clofarabine
Drug: Clofarabine, Etoposide, Mitoxantrone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clofarabine, Etoposide, and Mitoxantrone for Relapsed and Refractory Acute Leukemias

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Establish toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias [ Time Frame: Days 30-45 ] [ Designated as safety issue: Yes ]
  • Establish dose limiting toxicity of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias [ Time Frame: Days 30-45 ] [ Designated as safety issue: Yes ]
  • Establish maximum tolerated dose recommend Phase 2 dose of Clofarabine in combination with Etoposide and Mitoxantrone for therapy of relapsed or refractory acute leukemias [ Time Frame: Days 30-45 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Observe response of relapsed or refractory acute leukemias to therapy with these agents. [ Time Frame: 30-70 days ] [ Designated as safety issue: Yes ]
  • Assess the impact of Clofarabine interacting with Etoposide and Mitoxantrone in induction of DNA strand breaks [ Time Frame: 30-45 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Plan
Three patients will be enrolled at a given dose level. If one of these patients experiences a dose limiting toxicity (DLT), an additional three patients will be enrolled at the given dose level. Dose escalation may proceed if < 2/6 patients at a given dose level experience a DLT. If > 2/6 patients experience a DLT at a given dose level, the next lower dose level (dose given prior to toxicity) will be considered the recommended phase 2 dose.
Drug: Etoposide, Mitoxantrone, Clofarabine
Cohort 1: Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (3 doses); Clofarabine (Days 2-6)20 mg/m2. Cohort 2:Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (3 doses); Clofarabine (Days 2-6)25 mg/m2 Cohort 3: Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (3 doses); Clofarabine (Days 2-6)30 mg/m2. Cohort 4: Etoposide (Days 1-5) 100 mg/m2; Mitoxantrone (Days 1-3) 8 mg/m2 (5 doses); Clofarabine (Days 2-6)30 mg/m2. In the event of excessive DLT in Cohort 1, a Cohort 0 will be explored: Cohort 0: Etoposide (Days 1-5) 100 mg/m2
Other Names:
  • Clolar
  • Mitoxantrone hydrochloride
Experimental: Retreatment
Once a maximum tolerated dose is established, an expanded cohort will be enrolled at that dose for a total of 15 patients to determine a recommended phase 2 dose.
Drug: Clofarabine, Etoposide, Mitoxantrone
Retreatment doses should be as follows: Cohort 1: Etoposide (Days 1-4) 100 mg/m2; Mitoxantrone (Days 1-2) 8 mg/m2 (2 doses); Clofarabine (Days 1-4)20 mg/m2. Cohort 2:Etoposide (Days 1-4) 100 mg/m2; Mitoxantrone (Days 1-2) 8 mg/m2 (2 doses); Clofarabine (Days 1-4)25 mg/m2; Cohort 3: Etoposide (Days 1-4) 100 mg/m2; Mitoxantrone (Days 1-2) 8 mg/m2 (2 doses); Clofarabine (Days 1-4)30 mg/m2. Cohort 4: Etoposide (Days 1-4) 100 mg/m2; Mitoxantrone (Days 1-4) 8 mg/m2 (4 doses); Clofarabine (Days 1-4)30 mg/m2; Cohort 0: Etoposide (Days 1-4) 100 mg/m2; Mitoxantrone (Days 1-2) 8 mg/m2; Clofarabine (Days 1-4) 10 mg/m2.
Other Names:
  • Clolar
  • Mitoxantrone hydrochloride

Detailed Description:

This will be a phase I study with a standard 3x3 design. Patients will proceed to treatment through a series of cohorts with the three drugs being delivered over five days beginning with a dose of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-3, and clofarabine at 20 mg/m2 IV on days 2-6. Presuming this and subsequent cohorts are tolerable and no more than 1 patient per cohort develops DLT, MTD patients will be treated in cohorts of 3-6 patients up to a final dose level of Etoposide 100 mg/m2 on days 1-5,Mitoxantrone 8 mg/m2 days 1-5, and Clofarabine at 30 mg/m2 IV on days 2-6. Patients failing to enter remission may receive 4 days of therapy with Etoposide 100 mg/m2 on days 1-4,Mitoxantrone 8 mg/m2 days 1-2 or 1-4,and Clofarabine at 20-30 mg/m2 IV on days 1-4. According to established definitions for dose limiting toxicity a recommended phase II dose will be established. After this is established the final cohort will be expanded to 15 patients.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00882076

Locations
United States, Pennsylvania
Penn State Hershey Cancer Institute
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: David F. Claxton, MD Penn State College of Medicine
  More Information

No publications provided

Responsible Party: David F. Claxton, MD, Professor of Medicine, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00882076     History of Changes
Other Study ID Numbers: PSHCI 08-096
Study First Received: April 15, 2009
Last Updated: January 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
acute lymphoblastic leukemia
chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Etoposide
Mitoxantrone
Etoposide phosphate
Clofarabine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 28, 2014