Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning

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.

Conditions

• Leukemia
• Acute Myeloid Leukemia
• Acute Lymphocytic Leukemia
• Chronic Myeloid Leukemia
• Chronic Lymphocytic Leukemia
• Myeloproliferative Diseases
• Non-Hodgkins Lymphoma
• Hodgkins Lymphoma
• Multiple Myeloma
• Myelodysplastic Syndrome

Interventions

DRUG

Fludarabine monophosphate

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

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.

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.

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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center

  lead OTHER

Principal Investigators

• Uday Popat, MD · M.D. Anderson Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

5 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-04-11

Primary Completion

2022-08-11

Completion

2022-08-11

FDA Drug

Yes

Countries

• United States

Study Locations