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Safety and Efficacy of Gemtuzumab Ozogamicin (Mylotarg®) as for Treatment of Patients With CD33-Positive Acute Myeloid Leukemia (AML)


N/A
18 Years
N/A
Not Enrolling
Both
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Promyelocytic Leukemia (M3), Recurrent Adult Acute Myeloid Leukemia

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Trial Information

Safety and Efficacy of Gemtuzumab Ozogamicin (Mylotarg®) as for Treatment of Patients With CD33-Positive Acute Myeloid Leukemia (AML)


PRIMARY OBJECTIVES:

I. To study safety and efficacy single agent Gemtuzumab Ozogamicin (Mylotarg®) as induction
therapy for patients with Acute Myeloid Leukemia (AML) who have relapsed after standard
treatments or who are not candidates for standard consolidation treatment after Daunorubicin
and cytosine arabinoside.

SECONDARY OBJECTIVES:

I. To correlate morbidity and mortality with the use of gemtuzumab (gemtuzumab ozogamicin)
to specific subtypes of leukemia.

II. To correlate gemtuzumab response to degree of cluster of differentiation (CD) 33
positivity.

III. To correlate FMS-Related Tyrosine Kinase 3 (FLT 3)/nucleophosmin (NPM) status and CD 33
positivity to gemtuzumab response.

IV. To document incidence of sinusoidal obstruction syndrome with the use of gemtuzumab.

OUTLINE:

Patients receive gemtuzumab ozogamicin intravenously (IV) over 2 hours on days 1 and 15.
Treatment continues for 28 days in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up monthly for 1 year.


Inclusion Criteria:



- Patients must have confirmed relapsed or refractory acute myeloid leukemia and not a
candidate for standard induction treatment after daunorubicin and cytosine
arabinoside OR acute promyelocytic leukemia relapsed after all-trans retinoic acid
(ATRA) or Arsenic trioxide therapy

- Patients must have an initial diagnosis of acute myeloid leukemia or biphenotypic
acute leukemia

- Patients must have CD33 positivity of >= 30%

- Eastern Cooperative Oncology Group (ECOG) performance status =< 3

- Karnofsky > 60%

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2 X institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 30
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- The effects of Mylotarg on the developing human fetus are unknown; for this reason
and because Mylotarg class agents are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients may not be receiving any other investigational agents for leukemia

- Patients with known untreated Hepatitis C because veno-occlusive disease and liver
enzyme abnormalities have been associated with Mylotarg

- Uncontrolled intercurrent illness including, but not limited to active liver disease,
ongoing or active sepsis requiring vasopressors or mechanical ventilation,
symptomatic congestive heart failure, or psychiatric illness/social situations that
would limit compliance with study requirements

- Pregnant women are excluded from this study because Mylotarg is a Class D agent with
the potential for teratogenic or abortifacient effects; because there is an unknown
but potential risk for adverse events in nursing infants secondary to treatment of
the mother with Mylotarg, breastfeeding should be discontinued if the mother is
treated with Mylotarg

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible because of the potential for pharmacokinetic interactions with
Mylotarg; in addition, these patients are at increased risk of lethal infections when
treated with marrow-suppressive therapy; appropriate studies will be undertaken in
patients receiving combination antiretroviral therapy when indicated

- Congestive Heart Failure (CHF) with an ejection fraction < 30%

- Glomerular filtration rate (GFR) < 30ml/min

- Active central nervous system (CNS) involvement of leukemia

- Philadelphia chromosome + acute lymphoblastic leukemia (ALL)

- Prior hematopoietic transplant in last 3 months

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Rate of serious adverse events

Outcome Description:

95% confidence interval will be calculated. Graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Outcome Time Frame:

Approximately 1 year

Safety Issue:

Yes

Principal Investigator

Leslie Ellis, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Comprehensive Cancer Center of Wake Forest University

Authority:

United States: Institutional Review Board

Study ID:

CCCWFU 22311

NCT ID:

NCT01548911

Start Date:

May 2012

Completion Date:

Related Keywords:

  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Promyelocytic Leukemia (M3)
  • Recurrent Adult Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Promyelocytic, Acute

Name

Location

Comprehensive Cancer Center of Wake Forest University Winston-Salem, North Carolina  27157-1082