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A Phase II Study of High-Dose Intravenous Busulfan Plus Melphalan With Allogeneic or Autologous Marrow or Peripheral Blood Progenitor Cell Transplantation for Lymphoid Malignancies or Multiple Myeloma

Phase 2
18 Years
65 Years
Not Enrolling
Multiple Myeloma, Lymphoma

Thank you

Trial Information

A Phase II Study of High-Dose Intravenous Busulfan Plus Melphalan With Allogeneic or Autologous Marrow or Peripheral Blood Progenitor Cell Transplantation for Lymphoid Malignancies or Multiple Myeloma

Busulfan and melphalan are both traditional alkylating agents that are designed to interfere
with the production of cancer cells at the DNA (deoxyribonucleic acid) and RNA (ribonucleic
acid) level.

Before you can start treatment on this study, you will have what are called "screening
tests". These tests will help the doctor decide if you are eligible to take part in the
study. You will have a complete physical exam, including routine blood (2-3 teaspoons) and
urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone
marrow biopsy. Women who are able to have children must have a negative blood pregnancy

If you are found to be eligible to take part in this study, you will be able to start
receiving chemotherapy treatment with busulfan and melphalan. Participants who agree to the
optional blood draws described above will at first receive a therapeutic "trial dose" of
busulfan by vein to test the blood levels over time. This therapeutic trial dose of
busulfan is about 25% (1 fourth) of the full therapeutic dose of the drug. This information
will be used to decide what the future high-dose busulfan treatments you receive will be.
If you do not agree to the optional blood draw, you will receive a fixed amount of high-dose
busulfan from the start.

On the 1st day of hospitalization, you will receive fluids by vein through a central venous
catheter. If you choose the optional busulfan dose for pharmacokinetic-based busulfan
dosing, you will receive the optional busulfan dose 9 days before stem cell infusion (Day
1), followed by a rest day on Day 2. If you choose to receive a fixed dose of busulfan,
busulfan will be injected through a central venous catheter over 3 hours, once a day, for
the next 4 days (Days 3-6, ending 3 days before the stem cell infusion day).

Patients receiving pharmacokinetic-based dosing of busulfan will also continue to receive
busulfan on Days 3-6. This will be followed by melphalan for all patients, given through
your central venous catheter over 30 minutes, once a day, for 2 days, on days 8 and 9. Your
stem cell infusion day will be on Day 10 of treatment.

Patients receiving 5 out of 6 antigen matched-related allogeneic stem cell transplants or
unrelated allogeneic stem cell transplants will also receive antithymocyte globulin (ATG),
by vein, on Days 7-9, up to one day before the stem cell infusion. This is given to decrease
the risk of GVHD and graft rejection in mismatched transplants.

On Day 10, healthy blood stem cells or bone marrow from the donor will be given through the
central catheter. This is your transplant date. You will also receive several other
medications to help the treatment work and to help prevent infections while your immune
system is weak. Tacrolimus and methotrexate will be given to decrease the risk of
graft-versus-host-disease (GVHD). GVHD occurs when the donor's immune cells fight the
patient's body. The tacrolimus will be started on the day before the transplant and will
continue for up to six months. Tacrolimus is given by vein at first and then by mouth when
you are able to eat. Methotrexate is given by vein on Days 11, 13, 16, and possibly on Day
21, up to 11 days after the transplant.

Please note that the treatment dates listed above were used to help explain your general
treatment plan. By standard medical convention, the day of stem cell infusion is always
listed as day zero. Therefore, the days listed above are different from the treatment plan
described in the protocol and abstract.

Sulfamethoxazole (Bactrim) or pentamidine will be given to fight bacteria. Bactrim is given
by mouth when the counts are good. Pentamidine is given by vein when the counts are low.
Acyclovir will be given at first by vein and then Valtrex (valacyclovir) will be given by
pill to decrease the risk of viral infections. Granulocyte colony-stimulating factor (G-CSF)
will be given to help the new bone marrow grow. It is given as an injection under the skin
after the transplant. It will continue until the white blood cells reach an acceptable
level. Overall, some of these drugs will be given for as long as 6 months or possibly
longer. Other medications may be necessary. If you are allergic to some of these drugs,
changes will be made.

You will be in the hospital for about 3-4 weeks. You will have checkups every day until
discharged from the hospital. You will then be seen in the outpatient clinic at least 3
times a week until your blood counts improve. You will be seen by your doctor at least every
week until 100 days after the bone marrow transplant. You must stay in Houston during this
time. After 100 days, you will return to the clinic according to your individual physician's

Some patients may need to receive spinal taps with instillation of chemotherapy several
times over the year after transplantation. This is only for patients with a previous
clinical history of leukemic involvement of the brain or high risk of developing leukemia
relapse in the brain. The spinal tap is performed in the clinic. You are given local
anesthetic at the lower back site, a small needle is inserted in the space between 2 spinal
bones, a small amount of fluid that bathes the brain (cerebrospinal fluid) is removed for
testing, and a small amount of chemotherapy is given.

Bone marrow samples will be taken at about 1 month and 3 months after the transplant. You
will also have a lung function test at 3 months after the transplant.

This is an investigational study. The FDA has approved all of the drugs used in this study
for use in stem cell transplantation. Up to 168 patients will take part in this study. All
will be enrolled at M. D. Anderson.

Inclusion Criteria:

- Patients with lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma
(primary refractory or recurrent), or multiple myeloma (beyond first complete
remission or unresponsive to therapy. Complete remission for multiple myeloma defined
by absence of detectable paraprotein in serum and/or urine by immunoelectrophoresis
or immunofixation, and < 5% plasma cells in the bone marrow), not qualifying for
treatment protocols of higher priority.

- Age 18 to 65 years of age.

- Adequate renal function as defined by estimated serum creatinine clearance > 50
ml/min and serum creatinine < 1.8 mg/dL.

- Adequate hepatic function, as defined by serum glutamic pyruvic transaminase (SGPT) <
3 * upper limit of normal; serum bilirubin and alkaline phosphatase < 2 * upper limit
of normal, or considered not clinically significant.

- Adequate pulmonary function with Forced expiratory volume in one second (FEV1),
forced vital capacity (FVC), and Capacity of the Lung for Carbon Monoxide (DLCO)>
50%. Exceptions may be allowed for patients with pulmonary involvement after
discussing with principal investigator (PI).

- Adequate cardiac function with left ventricular ejection fraction >/= 40%. No
uncontrolled arrhythmias or symptomatic cardiac disease.

- Zubrod performance score < 2.

- Patients receiving an allogeneic transplant must have an HLA matched, or one A, B, or
DR mismatched related donor. Unrelated donor must be matched at A, B, and DR (defined
as A, B serologic matched and DRB1 molecular matched). Donor must be willing to
donate peripheral blood or bone marrow progenitor cells.

- Patient and donor should be willing to participate in the study by providing written

- Female patient must not be pregnant and have negative pregnancy.

Exclusion Criteria:

- Patients with unresolved grade >/= 3 non-hematologic toxicity from previous therapy.
Patients with grade 2 toxicity will be eligible at the discretion of the PI.

- Patients with active Central Nervous System (CNS) disease.

- Evidence of acute or chronic active hepatitis or cirrhosis. If positive hepatitis
serology, discuss with Study Chairman and consider liver biopsy.

- Uncontrolled infection, including Human immunodeficiency virus (HIV) or Human
T-lymphotropic virus Type I (HTLV-1) infection.

- Patients who have had a previous autologous or allogeneic stem cell transplant during
the past year.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Average Overall Survival Time

Outcome Description:

Average number of years for survival post transplant where overall survival time is measured from date of transplant to disease progression or death for any reason.

Outcome Time Frame:

Baseline(transplantation) to disease progression or death for any reason, up to 6 years.

Safety Issue:


Principal Investigator

Partow Kebriaei, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

December 2004

Completion Date:

November 2010

Related Keywords:

  • Multiple Myeloma
  • Lymphoma
  • Multiple Myeloma
  • Hodgkin's Disease
  • Non-Hodgkin's Lymphoma
  • Leukemia
  • Lymphoma
  • Busulfan
  • Melphalan
  • Autologous bone marrow
  • BMT
  • Peripheral blood stem cell transplant
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



UT MD Anderson Cancer Center Houston, Texas  77030