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Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center Identifier:
First received: April 4, 2012
Last updated: December 19, 2016
Last verified: December 2016

The goal of this clinical research study is to learn if giving busulfan and fludarabine before a stem cell transplant can help control the disease better than the standard method in patients with leukemia, lymphoma, multiple myeloma, MDS, or MPD. In this study, 2 doses of busulfan will be given 2 weeks before a stem cell transplant followed by 4 doses of busulfan and fludarabine during the week before the stem cell transplant, rather than the standard method of giving 4 doses of busulfan and fludarabine only during the week before the stem cell transplant.

The safety of this combination therapy will also be studied.

Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplants.

Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.

Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Chronic Myeloid Leukemia
Chronic Lymphocytic Leukemia
Myeloproliferative Diseases
Non-Hodgkins Lymphoma
Hodgkins Lymphoma
Multiple Myeloma
Myelodysplastic Syndrome
Drug: Fludarabine monophosphate
Drug: Busulfan
Procedure: Stem Cell Infusion
Drug: Tacrolimus
Drug: Methotrexate
Drug: G-CSF
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Timed Sequential Busulfan in Combination With Fludarabine in Allogeneic Stem Cell Transplantation

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Non-Relapse Mortality Rate (NRM) [ Time Frame: 100 days ]
    Bayesian monitoring rules monitor the 100-day NRM rate. Proportion of patients with NRM reported for each treatment arm, along with 95% Bayesian credible intervals. Bone marrow aspiration to check status of the disease around Day 30, and about 3, 6, and 12 months after the transplant.

Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Day 30 ]
    Progression-free survival calculated from the time of transplant by the method of Kaplan and Meier. Cox proportional hazards regression analysis used to assess the association between these survival parameters and clinical and treatment covariates of interest.

Estimated Enrollment: 200
Study Start Date: April 2012
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine + Busulfan

Fludarabine administered by vein at dose of 40 mg/m2 in 100 ml of normal saline (NS) on Days -6 through -3.

First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.

Drug: Fludarabine monophosphate
40 mg/m2 by vein on Days -6 through -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Busulfan
First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.
Other Names:
  • Busulfex
  • Myleran
Procedure: Stem Cell Infusion
Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.
Drug: Tacrolimus
Starting dose of 0.015 mg/kg (ideal body weight) as 24 hour continuous infusion daily adjusted to achieve therapeutic level of 5-15 ng/ml. Tacrolimus changed to oral dosing when tolerated and can be tapered off after day +90 if no graft versus host disease (GVHD) present.
Other Name: Prograf
Drug: Methotrexate
5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.
Drug: G-CSF
5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is > 500 * 10/L for 3 consecutive days.
Other Names:
  • Filgrastim
  • Neupogen

  Show Detailed Description


Ages Eligible for Study:   5 Years to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with high-risk hematologic malignancies with anticipated poor prognosis with non transplant therapy, including those in remission or with induction failure and after treated or untreated relapse. Diagnoses to be included a) Acute myeloid leukemia; b) Acute lymphocytic leukemia; c) Chronic myeloid leukemia; d) Chronic lymphocytic leukemia; e) Myelodysplastic syndrome; f) Myeloproliferative syndromes; g) Non-Hodgkins lymphoma; h) Hodgkins Lymphoma; i) Multiple myeloma.
  2. Patients must have a histocompatible stem cell donor. An HLA-identical related donor or a 8/8 matched unrelated donor.
  3. Age 5 to 75 years old.
  4. Performance score of >/= 70 by Karnofsky/Lansky or PS 0 to 1 (ECOG </=1).
  5. Left ventricular ejection fraction at least 40%.
  6. Adequate pulmonary function with FEV1, FVC and DLCO >/=50% of expected corrected for hemoglobin and/or volume. Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of >/= 92% on room air
  7. Creatinine clearance (calculated creatinine clearance is permitted) should be >40 ml/min.
  8. Bilirubin </= 2 x the upper limit of normal (except Gilbert's Syndrome). SGPT (ALT) < 200.
  9. Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
  10. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

Exclusion Criteria:

  1. HIV seropositivity.
  2. Uncontrolled infections.
  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 identifier: NCT01572662

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Uday Popat, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01572662     History of Changes
Other Study ID Numbers: 2011-0958
NCI-2012-00573 ( Registry Identifier: NCI CTRP )
Study First Received: April 4, 2012
Last Updated: December 19, 2016

Keywords provided by M.D. Anderson Cancer Center:
Acute myeloid leukemia
Acute lymphocytic leukemia
Chronic myeloid leukemia
Chronic lymphocytic leukemia
Myeloproliferative Diseases
Non-Hodgkins Lymphoma
Hodgkins lymphoma
Multiple myeloma
Myelodysplastic syndrome
Fludarabine monophosphate
Fludarabine phosphate
Stem cell transplant
Allogeneic Transplantation

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myeloproliferative Disorders
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions processed this record on May 22, 2017