Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning
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Purpose
The goal of this clinical research study is to learn if giving busulfan and fludarabine in different doses before a stem cell transplant can help control the disease better than the standard method in patients with leukemia or MDS. 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 |
- 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.
- 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: | 100 |
| 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:
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 administered at dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 16,000 ± 12% µMol-min or 20000 ± 12% µMol-min based on the pharmacokinetic studies. Other Names:
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:
|
|
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 16,000 ± 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:
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 administered at dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 16,000 ± 12% µMol-min or 20000 ± 12% µMol-min based on the pharmacokinetic studies. Other Names:
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:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 5 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
- Patients must have a histocompatible stem cell donor. An HLA-identical related donor or a 8/8 matched unrelated donor.
- Age 5 to 75 years old.
- Performance score of >/= 70 by Karnofsky/Lansky or PS 0 to 1 (ECOG </=1).
- Left ventricular ejection fraction at least 40%.
- Pulmonary function test (PFT) demonstrating a diffusion capacity greater than 50% predicted. Children unable to perform pulmonary function tests (e.g., less than 7 years old) pulse oximetry of >/= 92% on room air.
- Creatinine clearance (calculated creatinine clearance is permitted) should be >40 ml/min.
- Bilirubin </= 2 x the upper limit of normal (except Gilbert's Syndrome). SGPT (ALT) < 200.
- 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.
- Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
Exclusion Criteria:
- HIV seropositivity.
- Uncontrolled infections.
Contacts and Locations| Contact: Uday Popat, MD | 713-792-8750 |
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| 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 |
| Study First Received: | April 4, 2012 |
| Last Updated: | May 9, 2013 |
| 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:
|
Hodgkin Disease Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive 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 Leukemia, B-Cell Bone Marrow Diseases Hematologic Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hemorrhagic Disorders |
ClinicalTrials.gov processed this record on June 18, 2013