Study of VELCADE® With Mitoxantrone and Etoposide for Leukemias

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT00410423
First received: December 11, 2006
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

Based on what is known about it's mechanism of action, bortezomib is presumed to make other chemotherapy drugs work better. This study examines the use of bortezomib in combination with an already effective chemotherapy regimen that is used to treat leukemias that have relapsed or been refractory to treatment.


Condition Intervention Phase
Relapsed Acute Leukemia
Refractory Acute Leukemia
Drug: Bortezomib with mitoxantrone, etoposide and cytarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • Complete Remission [ Time Frame: 30-90 days ] [ Designated as safety issue: Yes ]
  • Partial Remission [ Time Frame: 30-90 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: January 2006
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib
Bortezomib in combination with mitoxantrone, etoposide and cytarabine
Drug: Bortezomib with mitoxantrone, etoposide and cytarabine
All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.
Other Name: Velcade

Detailed Description:

VELCADE is a drug that blocks growth of cancer cells and helps destroy them. This research will help us to determine if VELCADE when combined with chemotherapy is useful in treating the leukemia with which you have been diagnosed. Your leukemia is a type that did not respond to chemotherapy or has come back after successful therapy.

VELCADE is approved by the Food and Drug Administration (FDA) for the treatment of multiple myeloma for patients that have received at least one prior therapy. Multiple Myeloma is a type of cancer that develops from blood cells. The dose of the drug being used in this research study is the same as what is used for the treatment of myeloma but the number of injections is less. VELCADE has, however not been approved by the FDA for use in acute leukemia. Mitoxantrone and etoposide, the other two chemotherapy drugs are also used for treating leukemia.

In the first part of the study, we are going to test the safety of VELCADE at different doses when given with mitoxantrone and etoposide. You may be enrolled at any one of three doses. In the second part, we are going to assess the response to the combination of VELCADE and chemotherapy drugs. You will receive VELCADE at the chosen dose based on safety assessment from Phase I. It will be administered as an intravenous (through the vein) injection on day-1 and day-4 of the 5-day schedule. In addition, you will also receive mitoxantrone over 15 minutes and etoposide over 45 minutes from days 1-5. The first 28 days from the beginning of the treatment will be called a treatment cycle.

On day-14 of the treatment cycle, you will have a bone marrow biopsy done to see if all the leukemia cells have disappeared. If there is no evidence of leukemia, then you may receive growth factors to help your marrow recover faster. If there is still presence of leukemia, in the same amount or more, then the treatment will be considered a failure and you will not receive any more of this treatment.

If there is a partial improvement then you will receive additional cycles of VELCADE with chemotherapy as described above until there are no signs of your disease. This is called a complete remission.

Therapy will be withheld at any time if there is concern that you are having side-effects that are not medically acceptable. Once the side-effects have resolved, VELCADE therapy may be re-started at a lower dose.

It is estimated that you may require about two to three cycles of therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.
  • Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) will be eligible for the study.

    • Patients must have failed initial therapy that may manifest in either of the following ways:

      • Demonstration of Primary Refractory Disease (Primary Induction Failure) as evidenced by a mid-cycle bone marrow analysis showing lack of complete tumor clearance (CTC).
      • Relapse of initial disease after a period of attaining complete remission.
  • Patients must be > 18 years of age, with no upper age limit.
  • ECOG performance status of 0 or 1.
  • Patients have no symptomatic cardiac or pulmonary disease and adequate hepatic and renal function as measured by the following criteria:

    • Cardiac: Left ventricular ejection fraction at rest must be >40% (MUGA preferred)
    • Hepatic: ALT and AST < 3x the upper limits of normal range as specified by the institution's clinical laboratory.
    • Renal: Serum creatinine within the normal range (< 1.4 mg/dL) or if creatinine outside normal range then creatinine clearance > 60 mL/min/m2
  • Patients who have had a diagnosis of Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) will be eligible for the study.
  • Patients must have failed initial therapy that may manifest in either of the following ways:

    • Demonstration of Primary Refractory Disease (Primary Induction Failure) as evidenced by a mid-cycle bone marrow analysis showing lack of complete tumor clearance (CTC).
    • Relapse of initial disease after a period of attaining complete remission.
  • Patients must be > 18 years of age, with no upper age limit.
  • ECOG performance status of 0 or 1.
  • Patients have no symptomatic cardiac or pulmonary disease and adequate hepatic and renal function as measured by the following criteria:

    • Cardiac: Left ventricular ejection fraction at rest must be >40% (MUGA preferred)
    • Hepatic: ALT and AST < 3x the upper limits of normal range as specified by the institution's clinical laboratory.
    • Renal: Serum creatinine within the normal range (< 1.4 mg/dL) or if creatinine outside normal range then creatinine clearance > 60 mL/min/m2

Exclusion Criteria:

  • Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum or urinary pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient has received other investigational drugs within 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical 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: NCT00410423

Contacts
Contact: Joanne Filicko-O'Hara, MD 215-955-8874
Contact: Clinical Research Management Office 215-955-1661

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Joanne Filicko-O'Hara, MD    215-955-8874      
Contact: Clinical Research Management Office    215-955-1661      
Principal Investigator: Joanne Filicko-O'Hara, MD         
Sub-Investigator: Emmanuel Besa, MD         
Sub-Investigator: Matthew Carabasi, MD         
Sub-Investigator: Neal Flomenberg, MD         
Sub-Investigator: Dolores Grosso, DNP, CRNP         
Sub-Investigator: John Wagner, MD         
Sub-Investigator: Margaret Kasner, MD         
Sub-Investigator: Mark Weiss, MD         
Sub-Investigator: S. Onder Alpdogan, MD         
Sponsors and Collaborators
Thomas Jefferson University
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Joanne Filicko-O'Hara, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT00410423     History of Changes
Other Study ID Numbers: 06U.70, 2005-74
Study First Received: December 11, 2006
Last Updated: June 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Thomas Jefferson University:
Leukemia
Acute Myeloid Leukemia
Acute Lymphoid / Lymphoblastic Leukemia

Additional relevant MeSH terms:
Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Cytarabine
Etoposide phosphate
Bortezomib
Etoposide
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 26, 2014