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A Phase II Study of Subcutaneous Bortezomib as Maintenance Therapy for Patients With High-risk Acute Myeloid Leukemia in Remission


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Promyelocytic Leukemia (M3), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Secondary Acute Myeloid Leukemia

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Trial Information

A Phase II Study of Subcutaneous Bortezomib as Maintenance Therapy for Patients With High-risk Acute Myeloid Leukemia in Remission


PRIMARY OBJECTIVES:

I. To determine if bortezomib when given as maintenance therapy for six months
post-remission can improve the progression-free survival (PFS) rate by 50% (or 4.5 months)
in first remission patients with high-risk AML.

SECONDARY OBJECTIVES:

I. To determine the overall survival (OS) after maintenance therapy with bortezomib in first
remission AML patients.

II. To assess the safety and tolerability of subcutaneous (SC) administration of bortezomib
given as maintenance therapy to first remission AML patients.

OUTLINE:

Patients receive bortezomib SC on days 1, 8, 15 and 22. Treatment repeats every 35 days for
up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, every 3 months for
2 years, and then annually for 3 years.


Inclusion Criteria:



- All adults with first remission AML including those with prior myelodysplasia
(MDS)/AML, therapy-related AML, AML with trilineage dysplasia (AML-TLD), and AML with
adverse cytogenetics

- History of histopathologically documented AML that is currently in first remission
with the presence of 5% or less blasts by morphology and/or flow cytometry from a
bone marrow aspirate and/or biopsy obtained within 14 days of enrollment

- Patients must start therapy between 3-8 weeks after receiving their last prior
therapy (either induction therapy or consolidation therapy)

- Patients may receive up to 4 courses of remission consolidation therapy (e.g.,
cytarabine) prior to enrollment

- Normal kidney and liver function with serum creatinine =< 2.0 mg/dl

- Total bilirubin =< 1.5 upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

- Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree
to 1 of the following: practice effective barrier contraception during the entire
study treatment period and through a minimum of 30 days after the last dose of study
drug, or completely abstain from heterosexual intercourse

- Female subject is either postmenopausal for at least 1 year before the screening
visit, is surgically sterilized or if they are of childbearing potential, agree to
practice 2 effective methods of contraception from the time of signing the informed
consent form through 30 days after the last dose of bortezomib, or agree to
completely abstain from heterosexual intercourse

- Understand and voluntarily sign the informed consent form for this study

Exclusion Criteria:

- Favorable AML features defined as the following:

- t(8;21)(q22;q22); RUNX1-RUNX1T1

- inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11

- Mutated NPM1 without FLT3-ITD (normal karyotype)

- Mutated CEBPA (normal karyotype)

- Persistent clinically significant non-hematological toxicity that is > Grade 1 by
National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
v4 from prior chemotherapy

- Active uncontrolled infection

- Known infection with human immunodeficiency virus (HIV)

- Medical condition, serious concurrent illness, or other extenuating circumstance
that, in the judgment of the Principal Investigator, could jeopardize patient safety
or interfere with the objectives of the study

- Uncontrolled or significant cardiovascular disease, including:

- Uncontrolled angina or myocardial infarction within 6 months

- Current or history of congestive heart failure New York Heart Association (NYHA)
class 3 or 4, unless a screening echocardiogram (ECHO) or Multiple Gate
Acquisition Scan (MUGA) performed within 1 month prior to study screening
results in a left ventricular ejection fraction (LVEF) that is >= 45% (or
institutional lower limit of normal value)

- Prolonged QTc interval (> 450 msec)

- Diagnosed or treated for another malignancy within 3 years of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

- Patient has a platelet count of < 30,000 within 3 days before enrollment

- Patient has an absolute neutrophil count of < 300 within 3 days before enrollment

- Patient has >= Grade 2 peripheral neuropathy

- Patient has hypersensitivity to bortezomib, boron, or mannitol

- Female patients who are lactating or have a positive urine pregnancy test during the
screening; pregnancy testing is not required for postmenopausal or surgically
sterilized women

- Participation in clinical trials with other investigational agents not included in
this trial, within 14 days of the start of this trial and throughout the duration of
this trial

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival (PFS) after bortezomib maintenance therapy among patients with AML in remission

Outcome Time Frame:

Up to 2 years

Safety Issue:

No

Principal Investigator

John Pagel

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2529.00

NCT ID:

NCT01465386

Start Date:

November 2011

Completion Date:

Related Keywords:

  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Promyelocytic Leukemia (M3)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Secondary Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Promyelocytic, Acute
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109