Clinical trial · Interventional
Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning
Phase II Study of Timed Sequential Busulfan in Combination With Fludarabine in Allogeneic Stem Cell Transplantation
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (10)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Lymphocytic Leukemia | Acute Lymphoblastic Leukemia | ALIAS | 0.90 |
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Chronic Lymphocytic Leukemia | Chronic Lymphocytic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Chronic Myeloid Leukemia | Chronic Myeloid Leukemia, BCR-ABL1 Positive | ALIAS | 0.90 |
| Hodgkins Lymphoma | Hodgkin Lymphoma | ALIAS | 0.90 |
| Leukemia | Leukemia | ONTOLOGY_EXACT | 0.90 |
| Multiple Myeloma | Multiple Myeloma | CURATED_EXACT | 0.92 |
| Myelodysplastic Syndrome |
Interventions
Interventions (6)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Busulfan | Drug | Busulfan | ALIAS |
| Fludarabine monophosphate | Drug | — | UNRESOLVED |
| G-CSF | Drug | — | UNRESOLVED |
| Methotrexate | Drug | Methotrexate | ALIAS |
| Stem Cell Infusion | Procedure | — | UNRESOLVED |
| Tacrolimus | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Fludarabine + Busulfan
- description
- 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.
- interventionNames
- Drug: Fludarabine monophosphate
- Drug: Busulfan
- Procedure: Stem Cell Infusion
- Drug: Tacrolimus
- Drug: Methotrexate
- Drug: G-CSF
Primary outcomes (1)
- measure
- Non-Relapse Mortality Rate (NRM)
- timeFrame
- 100 days
- description
- Number of participants expired within the first 100 days after transplant not due to relapsed disease.
Secondary outcomes (2)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 5 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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.
References
Publications (1)
- DERIVEDPopat UR, Mehta RS, Bassett R, Chen J, Valdez BC, Kawedia J, Ahmed S, Alousi AM, Anderlini P, Al-Atrash G, Bashir Q, Ciurea SO, Hosing CM, Im JS, Jones R, Kebriaei P, Khouri I, Marin D, Nieto Y, Olson A, Oran B, Parmar S, Rezvani K, Qazilbash MH, Shah N, Srour SA, Shpall EJ, Champlin RE, Andersson BS. Fludarabine with a higher versus lower dose of myeloablative timed-sequential busulfan in older patients and patients with comorbidities: an open-label, non-stratified, randomised phase 2 trial. Lancet Haematol. 2018 Nov;5(11):e532-e542. doi: 10.1016/S2352-3026(18)30156-X. PMID 30389035