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

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00822770
First received: January 13, 2009
Last updated: June 13, 2014
Last verified: June 2014
  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 acute myeloblastic leukemia (AML), myelodysplastic syndromes (MDS), or Chronic myelogenous leukemia (CML).


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:


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

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) Plerixafor [ Time Frame: 28 day cycle (Plerixafor Day -7 to Day -4) ] [ Designated as safety issue: Yes ]
    MTD dose of Plerixafor in combination with a fixed dose of Filgrastim where dose limiting toxicity defined as any grade 4 non-hematologic toxicity observed within 28 days from Day 0 (day of transplant).


Secondary Outcome Measures:
  • Time to Failure [ Time Frame: Baseline till disease progression/death, up to 1 year. ] [ Designated as safety issue: No ]
    Time to treatment failure defined as either disease recurrence or death, measured in months.

  • Response Rate (Engraftment Versus Graft Failure) [ Time Frame: 100 Days post engraftment ] [ Designated as safety issue: No ]
    Engraftment: first day of three (3) consecutive days that Absolute neutrophil count (ANC) exceeds 0.5 X 109/L. Subsequent chimerism studies must demonstrate the presence of donor derived cells. Graft Failure: failure to achieve an ANC >0.5 X 109/L for 3 consecutive days within 28 days after transplantation or a decline of ANC <0.5 x 109/L for three consecutive days after initial documented engraftment unless this is correlated with progression / recurrence of the underlying malignancy.


Enrollment: 47
Study Start Date: January 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (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: Maximum Tolerated Dose (MTD) 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 + MTD 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: Maximum Tolerated Dose (MTD) 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:

  1. Patients age >/=18 to </= 65 years.
  2. 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.
  3. White Blood Count (CBC) </= 20 * 10^9/l.
  4. 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.
  5. Zubrod performance status 0 or 1, or Karnofsky performance status 90-100%.
  6. Left ventricular ejection fraction >/= 45 %. No uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease.
  7. 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.
  8. Serum creatinine </=1.5 mg/dl.
  9. Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml unless related to the malignancy.
  10. Total serum bilirubin </=1.5 mg/dl (unless Gilbert's syndrome) and alkaline phosphatase </=2.5 times laboratory standard upper limit of normal (ULN).
  11. Patient or patient's legal representative able to sign informed consent.

Exclusion Criteria:

  1. History of HIV positive.
  2. Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
  3. Pleural/pericardial effusion or ascites estimated >/= 1 liter.
  4. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy.
  5. History of acute hepatitis, chronic active hepatitis or cirrhosis.
  6. Patients with class 3 or 4 angina (New York Heart Association (NYHA) criteria).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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, a Sanofi Company
Investigators
Principal Investigator: Marina Konopleva, MD, PhD UT MD Anderson Cancer Center
  More Information

Additional Information:
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
Results First Received: June 13, 2014
Last Updated: June 13, 2014
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 July 23, 2014