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

NCT00990054 | Completed Phase 1 DMC

• 1 other identifier: MOZ04808
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this research study is to determine if plerixafor can make cells more sensitive to killing by cytarabine and daunorubicin, an anti-cancer drug regimen referred to as "7+3" that is commonly used in treating acute myeloid leukemia (AML). In this study, plerixafor is used with treatments cytarabine and daunorubicin and with and without granulocyte-colony stimulating factor (GCSF). Subjects will be monitored to see how well they tolerate the use of these drugs together and how well they work to treat the leukemia. The purpose of the study is to determine the maximum tolerated dose (MTD) per plerixafor dosing schedule (once daily \[QD\] or twice daily \[BID\]), and/or recommended phase 2 dose (RP2D), by assessing safety and tolerability of plerixafor (Mozobil®) when used in combination with cytarabine and daunorubicin, and with and without granulocyte-colony stimulating factor (G-CSF)

Conditions

Acute Myeloid Leukemia

Keywords

Cytarabine,; Daunorubicin,; De Novo,; Acute Myeloid Leukemia,; AML

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose of plerixafor when used in combination with cytarabine and daunorubicin and with and without GCSF

  28 days from first dose and up to 42 days following last dose

Secondary Outcomes (9)

• Anti-leukemia activity of plerixafor when used with cytarabine and daunorubicin

  Beginning at Day 14 and then until complete remission (CR), complete remission with incomplete count recovery (CRi), or treatment failure (TF)

• Maximal plasma concentration (Cmax) of plerixafor when used with cytarabine and daunorubicin

  Cycle 1 (1 week)

• Time to maximal plasma concentration (Tmax) of Plerixafor when used with cytarabine and daunorubicin

  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

  Cycle 1 (1 week)

• Area under the concentration-time curve over the dosing interval (τ) (AUC 0-τ) of plerixafor when used with cytarabine and daunorubicin

  Cycle 1 (1 week)

Study Arms (1)

plerixafor

EXPERIMENTAL

Drug: Plerixafor

Interventions

Plerixafor DRUG

240 mcg/kg/dose and proceeding to escalating dose levels for determination of the single-dose maximum tolerated dose (MTD) provided that there are no unacceptable dose limiting toxicities

Also known as: AMD3100, Mozobil

plerixafor

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 δ 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) δ2.5 - 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.

You may not qualify if:

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

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (8)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Ann Arbor, Michigan, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Rochester, New York, United States

Location

Unknown Facility

Cleveland, Ohio, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2009
• First Posted: October 6, 2009
• Study Start: December 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 24, 2015

Record last verified: 2015-03

Locations

US (8)