Study of Plerixafor Combined With Cytarabine and Daunorubicin in Patients With Newly Diagnosed Acute Myeloid Leukemia

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00990054
• Date of registration: 02/10/2009
• Primary sponsor: Genzyme
• Public title: Study of Plerixafor Combined With Cytarabine and Daunorubicin in Patients With Newly Diagnosed Acute Myeloid Leukemia
• Scientific title: A Phase I, Dose Escalation Study of Plerixafor in Combination With Cytarabine and Daunorubicin in Patients With Newly Diagnosed Acute Myeloid Leukemia
• Date of first enrolment: December 2009
• Target sample size: 36
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00990054
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Medical Monitor
• Affiliation: Genzyme

Key inclusion & exclusion criteria

Inclusion Criteria:

- Provide signed, dated informed consent prior to any protocol-specific procedures.

- Have a diagnosis of newly diagnosed AML, defined as >20% myeloblasts on the marrow
aspirate or peripheral blood differential, with or without extramedullary
involvement, with confirmatory immunophenotyping or immunocytochemistry (e.g.,
myeloperoxidase), documented within 14 days of enrollment.

- Have Eastern Cooperative Oncology Group (ECOG) performance status (Appendix A) score
of 0, 1, or 2.

- Toxicities from all prior treatments have resolved to baseline or d Grade 1 prior to
first dose of study drugs.

- Are surgically or biologically sterile or willing to practice acceptable birth
control, as follows: Females of child bearing potential must agree to abstain from
sexual activity or to use a medically approved contraceptive measure/regimen during
and for 3 months after the treatment period. Women of child bearing potential must
have a negative serum pregnancy test at the time of enrollment. Acceptable methods
of birth control include oral contraceptive, intrauterine device (IUD),
transdermal/implanted or injected contraceptives and abstinence.

- Males must agree to abstain from sexual activity or agree to utilize a
medially-approved contraception method during and for 3 months after the treatment
period.

- Have adequate renal and hepatic function, as indicated by the following laboratory
values: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) d2.5 -
upper limit of normal (ULN); Estimated creatinine clearance (CrCl) of > 50mL/min, as
calculated by the Cockcroft-Gault equation (Appendix F); total bilirubin =1.5-ULN
(except in patients with Gilbert Syndrome, in whom direct bilirubin must be
=1.5-ULN), International Normalized Ratio (INR) =1.5 after discontinuation of
anticoagulants.

- Have adequate cardiac function, as measured by left ventricular ejection fraction
(LVEF) =40% on echocardiography or multigated acquisition (MUGA) scan or similar
radionuclide angiographic scan.

- Be able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

- Have received previous systemic treatment for leukemia or antecedent hematologic
disorder (AHD), other than hydroxyurea or hematopoietic growth factors. Treatment
with hydroxyurea within 2 weeks of screening is allowed but must be discontinued at
least 24 hours prior to the first dose of study drugs.

- Have received prior treatment with plerixafor, cytarabine, or any anthracycline.

- Have a diagnosis of acute promyelocytic leukemia (APL), French-American-British (FAB)
classification M3 or World Health Organization (WHO) classification of APL with
t(15;17)(q(22;q12), or Bcr-Abl positive leukemia.

- For patients < 50 years of age, have cytogenetics associated with good prognosis
[(t(8;21)q(22;22), t(15;17),inv(16)(p13;q22)]. (Testing for these mutations must be
performed on blood or Bone Marrow prior to study registration.

- Have had a hematopoietic stem cell transplant (HSCT).

- Have an absolute blast count of the following at the time of first dose of
chemotherapy, despite cytoreduction with hydroxyurea or leukapheresis:

1. >50 x 10^9/L for patients not enrolled in a G-CSF-containing cohort

2. >25 x 10^9/L for patients enrolled in a G-CSF-containing cohort

- Have central nervous system (CNS) leukemia (Only patients with suspected CNS leukemia
must undergo lumbar puncture.)

- Have any of the following within the last 12 months: unstable supraventricular
arrhythmia (e.g., hemodynamic instability) or has a pacemaker; Any ventricular
arrhythmia, other than occasional premature ventricular contractions; Congestive
heart failure (controlled or uncontrolled); Myocardial infarction, ischemia, stable
coronary artery disease, or angina; Uncontrolled hypertension; Syncope with either a
known cardiovascular or an unknown etiology.

- Have a pre-existing disorder predisposing the patient to serious or life-threatening
infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding
disorder, or cytopenias).

- Have the need for anticoagulant therapy.

- Have a significant medical or psychiatric disorder that would interfere with consent,
study participation, or follow-up.

- Have an active acute or chronic systemic fungal, bacterial, viral, or other infection
(i.e., exhibiting ongoing signs/symptoms related to the infection [except isolated
fever] and without improvement, despite appropriate antibiotics or other treatment).

- Have severe concurrent diseases (e.g., a history of serious organ dysfunction or
disease) that may place the patient at undue risk to undergo induction therapy per
protocol, or obscure assessments of drug safety.

- Have a diagnosis of prior malignancy unless disease-free for at least 5 years
following therapy with curative intent, with the following exceptions:

1. Patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, if
definitive treatment for the condition has been completed; or

2. Patients with organ-confined prostate cancer with no evidence of recurrent or
progressive disease based on prostate-specific antigen (PSA) values after
treatment with curative intent.

- Have known human immunodeficiency virus (HIV) positivity or evidence of active viral
hepatitis.

- Are pregnant or breastfeeding.

- Are known to have an allergy to any component of the study drug regimen



Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Acute Myeloid Leukemia

Intervention(s)

Drug: Plerixafor

Primary Outcome(s)

Determine the maximum tolerated dose of plerixafor when used in combination with cytarabine and daunorubicin and with and without GCSF [Time Frame: 28 days from first dose and up to 42 days following last dose]

Secondary Outcome(s)

Anti-leukemia activity of plerixafor when used with cytarabine and daunorubicin [Time Frame: Beginning at Day 14 and then until complete remission (CR), complete remission with incomplete count recovery (CRi), or treatment failure (TF)]

Area under the concentration-time curve from time zero to infinity (AUC 0-8 ) of plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Area under the concentration-time curve from time zero to the last observed concentration (AUC 0-last) of plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Area under the concentration-time curve over the dosing interval (t) (AUC 0-t) of plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Half-life (T½) of plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Maximal plasma concentration (Cmax) of plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Obtain preliminary data on safety , tolerability, PK, leukemia cell mobilization and anti-leukemia activity of plerixafor when used in conjunction with G-CSF, cyatarbine and daunorubicin. [Time Frame: Cycle 1 (1 week) and then until complete remission (CR), complete remission with incomplete count recovery (CRi), or treatment failure (TF)]

Time to maximal plasma concentration (Tmax) of Plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Volume of distribution (Vz/F for SC administration; Vz for IV administration); in the case of multiexponential disposition, volume of distribution at steady-state (Vss) will be calculated of plerixafor when used with cytarabine and daunorubicin [Time Frame: Cycle 1 (1 week)]

Secondary ID(s)

MOZ04808

Source(s) of Monetary Support

Please refer to primary and secondary sponsors