Gemcitabine Combined With Busulfan and Melphalan, With Hematopoietic Cell Transplantation, for Patients With Poor-prognosis Advanced Lymphoid Malignancies
18 Years
69 Years
Both
Leukemia, Lymphoma, Myeloma
Trial Information
Gemcitabine Combined With Busulfan and Melphalan, With Hematopoietic Cell Transplantation, for Patients With Poor-prognosis Advanced Lymphoid Malignancies
Busulfan and melphalan are designed to kill cancer cells by binding to DNA (the genetic
material of cells), which may cause cancer cells to die. They are commonly used in stem cell
transplantation.
Gemcitabine is designed to disrupt the growth of cancer cells, which may cause cancer cells
to die. It may help to increase the effect of busulfan and melphalan on the tumor cells, by
not allowing these cells to repair the DNA damage caused by busulfan or melphalan.
You will have apheresis done to collect some of your stem cells. Apheresis is the process of
removing part of the blood (such as platelets or white blood cells) from the body in order
to remove certain elements, such as stem cells. Then, the rest of the blood is returned back
to your body. Your stem cells will be put back in your body after you finish receiving
gemcitabine, busulfan, and melphalan. Apheresis will be done by a major vein through a
central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible tube that
will be placed into a large vein while you are under local anesthesia. Your doctor will
explain these procedures to you in more detail, and you will be required to sign a separate
consent form for each procedure.
If you are found to be eligible to take part in this study, you will be enrolled in a group
of at least 2 participants to begin receiving the study drugs. The dose of the study drugs
you receive will depend on when you enrolled in this study. If no intolerable side effects
occur in your group, researchers will continue to enroll participants at the next highest
dose level until the highest tolerable dose of the study drugs is found. The dose that you
receive will remain the same throughout this study.
Before you start to receive chemotherapy at treatment doses, you will be given a very small
test dose of busulfan. Blood (1 teaspoon) will be drawn to check the levels of the drug in
your blood at ten different timepoints (5-6 tablespoons total). This will help the study
staff calculate your treatment doses of this drug. If there is a schedule conflict and the
laboratory is not available for this testing, this procedure will not be performed. In that
case, you would receive an unchanging dose of busulfan during the treatment.
During Day 1 you will receive gemcitabine and busulfan by CVC.
On Days 2-4, you will receive busulfan.
On Day 5, you will not receive any study drugs.
On Day 6, you will receive gemcitabine followed by melphalan.
On Day 7, you will receive melphalan.
On Day 8, you will not receive any study drugs.
On Day 9, you will receive your autologous stem cells through a needle in your vein over
about 30-60 minutes.
If you have a B-cell cancer, you will receive rituximab (a treatment used for certain
lymphomas or chronic lymphocytic leukemia) as part of standard of care, 1 day after and
again 8 days after the infusion of the autologous cells.
As part of standard care, you will receive G-CSF (filgrastim) as an injection just under
your skin daily, starting 1 day after the transplant, until your blood cell levels return
to normal.
As part of standard care, you will receive a total of 6 doses of palifermin by vein. Three
(3) of the doses will be given before starting chemotherapy (with a 24-hour break between
the last dose of palifermin and the first dose of chemotherapy), and 3 doses will be given
after the last chemotherapy dose, starting on Day 0.
You will be taken off this study 100 days after the transplant. You may be taken off this
study early if the disease gets worse or you experience any intolerable side effects.
As part of standard care, you will remain in the hospital for about 3-4 weeks after
transplantation. After you are released from the hospital, you will continue as an
outpatient in the Houston area to be monitored for infections and transplant-related
complications.
This is an investigational study. Busulfan, gemcitabine, and melphalan are all FDA approved
and commercially available. The use of these study drugs together and the use of gemcitabine
at these dose levels is investigational. Up to 143 patients will take part in this study.
All will be enrolled at M. D. Anderson.
Inclusion Criteria:
1. Age 18 - <70 years.
2. Patients with lymphoid malignancies who do not qualify for treatment protocols of
higher priority: 2.1) Primary refractory/recurrent Hodgkin's disease 2.2) Primary
refractory/recurrent non-Hodgkin's lymphoma 2.3) Multiple myeloma beyond first
remission or unresponsive to therapy, who do not qualify for higher priority
melphalan-based protocols.
3. Adequate renal function, as defined by estimated serum creatinine clearance >/= 50
ml/min and/or serum creatinine
4. Adequate hepatic function, as defined by SGOT and/or SGPT normal; serum bilirubin and alkaline phosphatase
5. Adequate pulmonary function with FEV1, FVC and DLCO >/= 50% of expected corrected for
hemoglobin or volume.
6. Adequate cardiac function with left ventricular ejection fraction >/= 40%. No
uncontrolled arrhythmias or symptomatic cardiac disease.
7. Zubrod performance status <2.
8. Patient should be willing to participate in the study by providing written consent.
9. Negative Beta HCG text in a woman with child-bearing potential, defined as not
post-menopausal for 12 months or no previous surgical sterilization
Exclusion Criteria:
1. Patients with grade >/= 3 non-hematologic toxicity from previous therapy that has not
resolved to grade 1.
2. Patients with prior whole brain irradiation
3. Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA
>=10,000 copies/mL, or >= 2,000 IU/mL).
4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic
hepatitis C or positive hepatitis C serology.
5. Active infection requiring parenteral antibiotics.
6. HIV infection, unless the patient is receiving effective antiretroviral therapy with
undetectable viral load and normal CD4 counts
7. Patients having received radiation therapy to head and neck (excluding eyes), and
internal organs of chest, abdomen or pelvis in the month prior to enrollment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum Tolerated Dose (MTD) of Gemcitabine with Busulfan + Melphalan.
Outcome Time Frame:
Continual reassessment: Baseline to Dose Limiting Toxicity, monitored daily during hospitalization, weekly to Day 30 and monthly to Day 100
Safety Issue:
Yes
Principal Investigator
Yago Nieto, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2006-0803
NCT ID:
NCT00410982
Start Date:
December 2006
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Myeloma
- Lymphoid Malignancies
- Hodgkin's Disease
- Non-Hodgkin's Lymphoma
- Acute Lymphoblastic Leukemia
- Chronic Lymphocytic Leukemia
- Hematopoietic Cell Transplantation
- Myeloma
- Leukemia
- Lymphoma
- Busulfan
- Busulfex
- Myleran
- Gemcitabine
- Gemcitabine Hydrochloride
- Gemzar
- Melphalan
- Alkeran
- Neoplasms
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
