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Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01572662
Recruitment Status : Active, not recruiting
First Posted : April 6, 2012
Last Update Posted : October 5, 2020
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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 or disease Intervention/treatment Phase
Leukemia 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Timed Sequential Busulfan in Combination With Fludarabine in Allogeneic Stem Cell Transplantation
Actual Study Start Date : April 2012
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2024

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 75 Years   (Child, Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01572662

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
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Principal Investigator: Uday Popat, MD M.D. Anderson Cancer Center
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT01572662    
Other Study ID Numbers: 2011-0958
NCI-2012-00573 ( Registry Identifier: NCI CTRP )
First Posted: April 6, 2012    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions