Study of VELCADE® With Mitoxantrone and Etoposide for Leukemias

NCT00410423 | Completed Phase 1 Results DMC

• 3 other identifiers: 06U.702005-74JT 1162
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed Acute Leukemia; Refractory Acute Leukemia

Keywords

Leukemia; Acute Myeloid Leukemia; Acute Lymphoid / Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose Limiting Toxicity in Phase I

  Dose limiting toxicity (DLT) is defined as grade-3 toxicity definitely related to bortezomib or grade-4 toxicity probably or definitely related to bortezomib.

  30-90 days

• Complete Response Rate to 1.3mg/m^2 of Bortezomib With Mitoxantrone and Etoposide in Phase II

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. The percentage of participants that experienced complete response will be reported.

  Up to 7 years

Study Arms (3)

Bortezomib 0.7mg/m^2

EXPERIMENTAL

Bortezomib in combination with mitoxantrone, etoposide and cytarabine

Drug: Bortezomib with mitoxantrone, etoposide and cytarabine

Bortezomib 1.0mg/m^2

EXPERIMENTAL

Drug: Bortezomib 1.0mg/m^2

Bortezomib 1.3mg/m^2

EXPERIMENTAL

Drug: Bortezomib 1.3mg/m^2

Interventions

Bortezomib with mitoxantrone, etoposide and cytarabine DRUG

All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.

Also known as: Velcade

Bortezomib 0.7mg/m^2

Bortezomib 1.0mg/m^2 DRUG

All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.

Also known as: Velcade

Bortezomib 1.0mg/m^2

Bortezomib 1.3mg/m^2 DRUG

All patients receive bortezomib in combination with mitoxantrone, etoposide and cytarabine. This is a 5 day chemotherapy regimen that is administered in the hospital.

Also known as: Velcade

Bortezomib 1.3mg/m^2

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Bortezomib; Mitoxantrone; Etoposide; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Joanne Filicko-O'Hara, MD
• Organization: Thomas Jefferson University

Joanne.Filicko@jefferson.edu

215-955-8874

Study Officials

• Joanne Filicko-O'Hara, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2006
• First Posted: December 12, 2006
• Study Start: January 1, 2006
• Primary Completion: May 1, 2013
• Study Completion: September 1, 2014
• Last Updated: April 30, 2025
• Results First Posted: April 17, 2018

Record last verified: 2025-04

Locations

US (1)