Clinical trial

Phase II Study of Timed Sequential Busulfan in Combination With Fludarabine in Allogeneic Stem Cell Transplantation

Name

2011-0958

Description

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.

Trial arms

Trial start

2012-04-11

Estimated PCD

2022-08-11

Trial end

2022-08-11

Status

Completed

Phase

Early phase I

Treatment

Fludarabine monophosphate

40 mg/m2 by vein on Days -6 through -3.

Arms:

Fludarabine + Busulfan

Other names:

Fludarabine Phosphate, Fludara

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.

Arms:

Fludarabine + Busulfan

Other names:

Busulfex, Myleran

Stem Cell Infusion

Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.

Arms:

Fludarabine + Busulfan

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.

Arms:

Fludarabine + Busulfan

Other names:

Prograf

Methotrexate

5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.

Arms:

Fludarabine + Busulfan

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.

Arms:

Fludarabine + Busulfan

Other names:

Filgrastim, Neupogen

Size

201

Primary endpoint

Non-Relapse Mortality Rate (NRM)

100 days

Eligibility 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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 201, 'type': 'ACTUAL'}}

Updated at

2023-06-29

1 organization

2 products

3 drugs

10 indications

Organization

M.D. Anderson Cancer Center

Product

Fludarabine

Indication

Leukemia