Plerixafor and Granulocyte Colony-stimulating Factor (G-CSF) With Busulfan, Fludarabine and Thymoglobulin
This study has been completed.
Sponsor:
M.D. Anderson Cancer Center
Collaborator:
Genzyme
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00822770
First received: January 13, 2009
Last updated: December 7, 2012
Last verified: December 2012
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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:
MedlinePlus related topics:
Acute Myeloid Leukemia
Bone Marrow Transplantation
Cancer
Leukemia
Myelodysplastic Syndromes
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:
- 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 ]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:
Drug: Fludarabine
Dose of 40 mg/m^2 beginning on Day -6 for four consecutive days.
Other Names:
Drug: Busulfan
Dose of 130 mg/m^2 for four consecutive days, immediately after completion of Fludarabine.
Other Names:
Procedure: Allogeneic blood stem cell transplant
Stem Cell Infusion (Bone marrow or PBPC)
Other Names:
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:
Drug: Fludarabine
Dose of 40 mg/m^2 beginning on Day -6 for four consecutive days.
Other Names:
Drug: Busulfan
Dose of 130 mg/m^2 for four consecutive days, immediately after completion of Fludarabine.
Other Names:
Procedure: Allogeneic blood stem cell transplant
Stem Cell Infusion (Bone marrow or PBPC)
Other Names:
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.
- White Blood Count (CBC) </= 20 * 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 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.
- 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 (New York Heart Association (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:
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: | December 7, 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, 2013