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

NCT00822770 | Completed Phase 1 Results

• 1 other identifier: 2007-0772
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Stem Cell Transplantation; Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Grade 4 Dose Limiting Toxicity to Determine Maximum Tolerated Dose (MTD) Plerixafor

  Phase I determination of 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).

  28 day cycle (Plerixafor Day -7 to Day -4)

Secondary Outcomes (2)

• Number of Participants Alive With no Disease Progression at Time of Allo Transplant

  Baseline till transplant, Day -9 to Day 0, to 10 days

• Engraftment Response Rate: Number of Transplanted Participants With Complete Chimerism at Day 30

  30 Days post engraftment

Study Arms (2)

Phase I

EXPERIMENTAL

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

Drug: Plerixafor; Drug: Filgrastim; Drug: Fludarabine; Drug: Busulfan; Procedure: Allogeneic blood stem cell transplant; Drug: ATG (Thymoglobulin)

Phase II

EXPERIMENTAL

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

Drug: Plerixafor; Drug: Filgrastim; Drug: Fludarabine; Drug: Busulfan; Procedure: Allogeneic blood stem cell transplant; Drug: ATG (Thymoglobulin)

Interventions

Plerixafor DRUG

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

Also known as: AMD3100

Phase I; Phase II

Filgrastim DRUG

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

Also known as: G-CSF, Neupogen

Phase I; Phase II

Fludarabine DRUG

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

Also known as: Fludarabine Phosphate, Fludara

Phase I; Phase II

Busulfan DRUG

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

Also known as: Busulfex™, Myleran®

Phase I; Phase II

Allogeneic blood stem cell transplant PROCEDURE

Stem Cell Infusion (Bone marrow or PBPC)

Also known as: Bone Marrow Transplantation, Blood Stem Cell Transplantation

Phase I; Phase II

ATG (Thymoglobulin) DRUG

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.

Also known as: Antithymocyte globulin

Phase I; Phase II

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Graft vs Host Disease

Interventions

plerixafor; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine; fludarabine phosphate; Busulfan; Bone Marrow Transplantation; thymoglobulin; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System 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; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Marina Konopleva, MD, PhD / Associate Professor
• Organization: The University of Texas (UT) MD Anderson Cancer Center

mkonople@mdanderson.org

713-794-1628

Study Officials

• Marina Konopleva, MD, PhD

  UT MD Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 13, 2009
• First Posted: January 14, 2009
• Study Start: January 1, 2009
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 14, 2020
• Results First Posted: July 16, 2014

Record last verified: 2020-09

Locations

US (1)