Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia

NCT00906945 | Completed Phase 1 Results DMC

• 1 other identifier: 10-0910 / 201106039
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 3

Brief Summary

This study is designed to test the combination of Plerixafor with G-CSF for chemosensitization in patients with relapsed or refractory AML.

Conditions

Leukemia, Myeloid, Acute

Keywords

stem cell mobilization; chemosensitization; CXCR4; SDF-1; CXCL-12

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC

  Completion of Phase I enrollment (17 months)

• Phase II: Complete Response Rate (CR+CRi)

  * Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1,000/mm3, platelet count \> 100,000/mm3. * Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia \<1,000/mm3 or thrombocytopenia \<100,000/mm3.

  45 days

Secondary Outcomes (12)

• Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency

  30 days following end of treatment

• Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery

  Up to 62 days after treatment

• Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery

  Up to 62 days after treatment

• Time to Hematologic Recovery as Measured by Time to Platelet Recovery

  Up to 62 days after treatment

• Time to Hematologic Recovery as Measured by Time to Platelet Recovery

  Up to 62 days after treatment

Study Arms (6)

Dose Level 1

EXPERIMENTAL

* G-CSF 10 mcg/kg SQ on Days 1-8 * Plerixafor 240 mcg/kg/d IV qd * Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8 * Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8 * Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

Drug: G-CSF; Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Dose Level 2

EXPERIMENTAL

* G-CSF 10 mcg/kg SQ on Days 1-8 * Plerixafor 320 mcg/kg/d IV qd * Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8 * Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8 * Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

Drug: G-CSF; Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Dose Level 3

EXPERIMENTAL

* G-CSF 10 mcg/kg SQ on Days 1-8 * Plerixafor 420 mcg/kg/d IV qd * Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8 * Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8 * Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

Drug: G-CSF; Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Dose Level 4

EXPERIMENTAL

* G-CSF 10 mcg/kg SQ on Days 1-8 * Plerixafor 560 mcg/kg/d IV qd * Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8 * Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8 * Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

Drug: G-CSF; Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Dose Level 5

EXPERIMENTAL

* G-CSF 10 mcg/kg SQ on Days 1-8 * Plerixafor 750 mcg/kg/d IV qd * Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8 * Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8 * Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

Drug: G-CSF; Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

MTD - Phase II

EXPERIMENTAL

* G-CSF MTD determined in Phase 1 SQ on Days 1-8 * Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd * Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8 * Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8 * Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8

Drug: G-CSF; Drug: Plerixafor; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Interventions

G-CSF DRUG

Also known as: filgrastim, Neupogen

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; MTD - Phase II

Plerixafor DRUG

Also known as: AMD3100, Mozobil

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; MTD - Phase II

Mitoxantrone DRUG

Also known as: Novantrone

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; MTD - Phase II

Etoposide DRUG

Also known as: VP-16, Vepesid, Etopophos

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; MTD - Phase II

Cytarabine DRUG

Also known as: Ara-C, Cytosar

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; MTD - Phase II

Eligibility Criteria

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

You may qualify if:

• Acute myeloid leukemia diagnosed by WHO criteria with one of the following:
• Primary refractory disease following no more than 2 cycles of induction chemotherapy
• First relapse with no prior unsuccessful salvage chemotherapy
• Age between 18 and 70 years old
• ECOG performance status ≤ 3
• Adequate organ function defined as:
• Calculated creatinine clearance ≥ 50 ml/min
• AST, ALT, total bilirubin ≤ 2 x ULN except when in the opinion of treating physician is due to direct involvement of leukemia (eg. hepatic infiltration or biliary obstruction due to leukemia)
• Left ventricular ejection fraction of ≥ 40% by MUGA scan or echocardiogram
• 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 or urine 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 medically approved contraception method during and for 3 months after the treatment period
• Able to provide signed informed consent prior to registration on study

You may not qualify if:

• Acute promyelocytic leukemia (AML with t(15;17)(q22;q11) and variants)
• Peripheral blood blast count ≥ 20 x 103 /mm3
• Active CNS involvement with leukemia
• Previous treatment with MEC or other regimen containing both mitoxantrone and etoposide
• Pregnant or nursing
• Received any other investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within the preceding 2 weeks
• Received colony stimulating factors filgrastim or sargramostim within 1 week or pegfilgrastim within 2 weeks of study
• Severe concurrent illness that would limit compliance with study requirements

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (3)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; plerixafor; Mitoxantrone; Etoposide; etoposide phosphate; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Geoffrey Uy, M.D.
• Organization: Washington University School of Medicine

guy@wustl.edu

314-454-8304

Study Officials

• Geoffrey L. Uy, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2009
• First Posted: May 21, 2009
• Study Start: February 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: September 1, 2015
• Last Updated: April 4, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-02

Locations

US (3)