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Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Relapsed Acute Leukemia, Refractory Acute Leukemia

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Trial Information

Phase I/II Trial of VELCADE® (Bortezomib) in Combination With Mitoxantrone and Etoposide for Relapsed or Refractory Acute Leukemias


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.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Remission

Outcome Time Frame:

30-90 days

Safety Issue:

Yes

Principal Investigator

Joanne Filicko-O'Hara, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thomas Jefferson University

Authority:

United States: Institutional Review Board

Study ID:

06U.70

NCT ID:

NCT00410423

Start Date:

January 2006

Completion Date:

January 2014

Related Keywords:

  • Relapsed Acute Leukemia
  • Refractory Acute Leukemia
  • Leukemia
  • Acute Myeloid Leukemia
  • Acute Lymphoid / Lymphoblastic Leukemia
  • Leukemia
  • Acute Disease

Name

Location

Thomas Jefferson University Philadelphia, Pennsylvania  19107-6541