Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01572662
First received: April 4, 2012
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

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
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

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: Randomized 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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: 150
Study Start Date: April 2012
Estimated Primary Completion Date: April 2017 (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.

Drug: Fludarabine monophosphate
40 mg/m2 by vein on Days -6 through -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Busulfan

80 mg/m2 by vein on Days -13 and -12. Pharmacokinetic (PK) studies will be done with the first dose.

Higher Dose Group: 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
Experimental: Fludarabine + Higher Dose 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.

Depending on randomization, Busulfan administered at dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min or 20000 ± 12% µMol-min based on pharmacokinetic studies.

Drug: Fludarabine monophosphate
40 mg/m2 by vein on Days -6 through -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Busulfan

80 mg/m2 by vein on Days -13 and -12. Pharmacokinetic (PK) studies will be done with the first dose.

Higher Dose Group: 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

  Eligibility

Ages Eligible for Study:   5 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT01572662

Contacts
Contact: Uday Popat, MD 713-792-8750

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Uday Popat, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01572662     History of Changes
Other Study ID Numbers: 2011-0958, NCI-2012-00573
Study First Received: April 4, 2012
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Acute myeloid leukemia
Acute lymphocytic leukemia
Chronic myeloid leukemia
Chronic lymphocytic leukemia
Myeloproliferative Diseases
Non-Hodgkins Lymphoma
Hodgkins lymphoma
Multiple myeloma
Myelodysplastic syndrome
MDS
Fludarabine monophosphate
Fludarabine phosphate
Fludara
Busulfan
Busulfex
Myleran
Tacrolimus
Prograf
Methotrexate
G-CSF
Filgrastim
Neupogen
Stem cell transplant
Allogeneic Transplantation

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

ClinicalTrials.gov processed this record on July 28, 2014