Plerixafor and Granulocyte Colony-stimulating Factor (G-CSF) With Busulfan, Fludarabine and Thymoglobulin - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Genzyme
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00822770

Purpose

The goal of this clinical research study is to learn about the safety of AMD3100 (plerixafor) and G-CSF (filgrastim) in combination with fludarabine, busulfan, and an allogeneic blood stem cell transplant. This treatment will be studied in patients with AML, MDS, or CML.

Objectives:

Primary Objective:

To determine the safety of Plerixafor and Filgrastim (G-CSF) in combination with busulfan, fludarabine and allogeneic hematopoietic transplantation for treatment of advanced myeloid leukemias.
Determine biologic effects of Plerixafor and G-CSF on leukemia cells.
To determine if the combination of Plerixafor and G-CSF with busulfan, fludarabine will improve progression free survival post allogeneic stem cell transplantation from an HLA-compatible donor compared to historical controls receiving busulfan-fludarabine alone.

Secondary Objectives:

1. To determine the time to engraftment, the rate and severity of GVHD, and immune reconstitution.

Condition	Intervention	Phase
Stem Cell Transplantation Leukemia	Drug: Plerixafor Drug: Filgrastim Drug: Fludarabine Drug: Busulfan Procedure: Allogeneic blood stem cell transplant Drug: ATG (Thymoglobulin)	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	G-CSF and Plerixafor With Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation for Myeloid Leukemias

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia

Drug Information available for: Busulfan Fludarabine Fludarabine phosphate Plerixafor Filgrastim Lenograstim Granulocyte colony-stimulating factor Antilymphocyte Serum

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Phase I: Maximum Tolerated Dose (MTD) [Plerixafor + Fixed Dose of Filgrastim] [ Time Frame: 28 day cycle (Plerixafor Day -7 to Day -4) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Phase I: Response Rate and Toxicity [ Time Frame: 28 days from Day 0 (day of transplant) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	72
Study Start Date:	December 2008
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Phase I ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant	Drug: Plerixafor Phase I: Starting dose of 0 (escalating doses 80, 160, 240 mcg/kg) given daily subcutaneously in abdomen for 4 doses. Phase II: Dose as determined in Phase I Other Name: AMD3100 Drug: Filgrastim Dose of 10 mcg/kg subcutaneous injection beginning on day -9 daily for 6 days. Other Names: G-CSF Neupogen Drug: Fludarabine Dose of 40 mg/m^2 beginning on Day -6 for four consecutive days. Other Names: Fludarabine Phosphate Fludara Drug: Busulfan Dose of 130 mg/m^2 for four consecutive days, immediately after completion of Fludarabine. Other Names: Busulfex™ Myleran® Procedure: Allogeneic blood stem cell transplant Stem Cell Infusion (Bone marrow or PBPC) Other Names: Bone Marrow Transplantation Blood Stem Cell Transplantation Drug: ATG (Thymoglobulin) Dose(s) of 0.5 mg/kg on day -3; of 1.5 mg/kg on day -2; and of 2 mg/kg on day -1. Given only to patients with unrelated donors. Other Name: Antithymocyte globulin
Experimental: Phase II ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant	Drug: Plerixafor Phase I: Starting dose of 0 (escalating doses 80, 160, 240 mcg/kg) given daily subcutaneously in abdomen for 4 doses. Phase II: Dose as determined in Phase I Other Name: AMD3100 Drug: Filgrastim Dose of 10 mcg/kg subcutaneous injection beginning on day -9 daily for 6 days. Other Names: G-CSF Neupogen Drug: Fludarabine Dose of 40 mg/m^2 beginning on Day -6 for four consecutive days. Other Names: Fludarabine Phosphate Fludara Drug: Busulfan Dose of 130 mg/m^2 for four consecutive days, immediately after completion of Fludarabine. Other Names: Busulfex™ Myleran® Procedure: Allogeneic blood stem cell transplant Stem Cell Infusion (Bone marrow or PBPC) Other Names: Bone Marrow Transplantation Blood Stem Cell Transplantation Drug: ATG (Thymoglobulin) Dose(s) of 0.5 mg/kg on day -3; of 1.5 mg/kg on day -2; and of 2 mg/kg on day -1. Given only to patients with unrelated donors. Other Name: Antithymocyte globulin

Arms

Assigned Interventions

Experimental: Phase I

ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant

Drug: Plerixafor

Phase I: Starting dose of 0 (escalating doses 80, 160, 240 mcg/kg) given daily subcutaneously in abdomen for 4 doses.

Phase II: Dose as determined in Phase I

Other Name: AMD3100

Drug: Filgrastim

Dose of 10 mcg/kg subcutaneous injection beginning on day -9 daily for 6 days.

Other Names:

G-CSF
Neupogen

Drug: Fludarabine

Dose of 40 mg/m^2 beginning on Day -6 for four consecutive days.

Other Names:

Fludarabine Phosphate
Fludara

Drug: Busulfan

Dose of 130 mg/m^2 for four consecutive days, immediately after completion of Fludarabine.

Other Names:

Busulfex™
Myleran®

Procedure: Allogeneic blood stem cell transplant

Stem Cell Infusion (Bone marrow or PBPC)

Other Names:

Bone Marrow Transplantation
Blood Stem Cell Transplantation

Drug: ATG (Thymoglobulin)

Dose(s) of 0.5 mg/kg on day -3; of 1.5 mg/kg on day -2; and of 2 mg/kg on day -1. Given only to patients with unrelated donors.

Other Name: Antithymocyte globulin

Experimental: Phase II

ATG + Plerixafor (AMD3100) + G-CSF (Filgrastim) + Fludarabine + Busulfan + Allogeneic blood stem cell transplant

Drug: Plerixafor

Phase I: Starting dose of 0 (escalating doses 80, 160, 240 mcg/kg) given daily subcutaneously in abdomen for 4 doses.

Phase II: Dose as determined in Phase I

Other Name: AMD3100

Drug: Filgrastim

Dose of 10 mcg/kg subcutaneous injection beginning on day -9 daily for 6 days.

Other Names:

G-CSF
Neupogen

Drug: Fludarabine

Dose of 40 mg/m^2 beginning on Day -6 for four consecutive days.

Other Names:

Fludarabine Phosphate
Fludara

Drug: Busulfan

Dose of 130 mg/m^2 for four consecutive days, immediately after completion of Fludarabine.

Other Names:

Busulfex™
Myleran®

Procedure: Allogeneic blood stem cell transplant

Stem Cell Infusion (Bone marrow or PBPC)

Other Names:

Bone Marrow Transplantation
Blood Stem Cell Transplantation

Drug: ATG (Thymoglobulin)

Dose(s) of 0.5 mg/kg on day -3; of 1.5 mg/kg on day -2; and of 2 mg/kg on day -1. Given only to patients with unrelated donors.

Other Name: Antithymocyte globulin

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients age >/=18 to </= 65 years.
Diagnosis of AML in first or greater remission, first or subsequent relapse, or primary induction failure; MDS with intermediate or high risk International Prognostic Scoring System (IPSS) score having failed to respond or recurred after chemotherapy; in remission or having active disease after treatment; AML arising from MDS; or CML which has failed to respond to imatinib or other tyrosine kinase inhibitor and has had >5% blasts in the blood or bone marrow. Patients receiving second transplants after relapse are considered in the relapse group.
WBC </= 20 x 10^9/l.
Patients should have a histocompatible, related or unrelated volunteer donor available. A histocompatible donor is defined as HLA matched related donor or an unrelated donor matched for HLA- A, B, C, and DR antigens by high-resolution DNA techniques.
Zubrod performance status 0 or 1, or Karnofsky performance status 90-100%.
Left ventricular ejection fraction >/= 45 %. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
No symptomatic pulmonary disease. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) >/= 50 % of expected, corrected for hemoglobin.
Serum creatinine </=1.5 mg/dl.
Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml unless related to the malignancy.
Total serum bilirubin </=1.5 mg/dl (unless Gilbert's syndrome) and alkaline phosphatase </=2.5 times laboratory standard upper limit of normal (ULN).
Patient or patient's legal representative able to sign informed consent.

Exclusion Criteria:

History of HIV positive.
Positive Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
Pleural/pericardial effusion or ascites estimated >/= 1 liter.
Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy.
History of acute hepatitis, chronic active hepatitis or cirrhosis.
Patients with class 3 or 4 angina (NYHA criteria).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00822770

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Genzyme

Investigators

Principal Investigator:

Marina Konopleva, MD, PhD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00822770 History of Changes
Other Study ID Numbers:	2007-0772
Study First Received:	January 13, 2009
Last Updated:	February 20, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Blood Stem Cell Transplantation
Bone Marrow Transplantation
Bone Marrow Cell Transplantation
Stem Cell Transplantation
Allogeneic Hematopoietic Transplantation
Advanced Myeloid Leukemia
Acute Myeloid Leukemia
AML
Myelodysplastic syndrome
MDS
Chronic Myeloid Leukemia
CML
Graft Versus Host Disease
GVHD

ATG
Busulfan
Busulfex™
Myleran®
Filgrastim
Neupogen
Fludarabine
Fludarabine Phosphate
Fludara™
G-CSF
Plerixafor
Antithymocyte globulin
Thymoglobulin

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Antilymphocyte Serum
Busulfan
Fludarabine monophosphate
Lenograstim
Fludarabine
Vidarabine
JM 3100
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Adjuvants, Immunologic
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on May 23, 2012