Gemcitabine Plus Busulfan, Melphalan and Hematopoietic Cell Transplant for Advanced Lymphoid Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00410982
First received: December 11, 2006
Last updated: September 24, 2012
Last verified: September 2012
  Purpose

The goal of this clinical research study is to find the highest tolerated dose of gemcitabine that can be given with busulfan and melphalan. The safety of this drug combination will also be studied.


Condition Intervention Phase
Leukemia
Lymphoma
Myeloma
Drug: Busulfan
Drug: Gemcitabine
Drug: Melphalan
Other: Hematopoietic Cell Transplantation
Drug: Rituximab for Patients with B-Cell Malignancies
Drug: Palifermin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gemcitabine Combined With Busulfan and Melphalan, With Hematopoietic Cell Transplantation, for Patients With Poor-prognosis Advanced Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Gemcitabine with Busulfan + Melphalan. [ Time Frame: Continual reassessment: Baseline to Dose Limiting Toxicity, monitored daily during hospitalization, weekly to Day 30 and monthly to Day 100 ] [ Designated as safety issue: Yes ]

Enrollment: 145
Study Start Date: December 2006
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine + Busulfan + Melphalan + HCT
HCT = Hematopoietic Cell Transplantation
Drug: Busulfan
Day -10 = 32 mg/m^2 Intravenous Test Dose; Days -8 thru -5 = 105 mg/m^2 Intravenous
Other Names:
  • Busulfex
  • Myleran
Drug: Gemcitabine
Day -8 = 75 mg/m^2 Intravenous bolus; Day -3 = 75 mg/m^2 Intravenous bolus.
Other Names:
  • Gemzar
  • Gemcitabine Hydrochloride
Drug: Melphalan
Day -3 and Day -2 = 60 mg/m^2 Intravenous.
Other Name: Alkeran
Other: Hematopoietic Cell Transplantation
Infusion of stem cells on Day 0.
Other Names:
  • Stem Cell Infusion
  • HCT
Drug: Rituximab for Patients with B-Cell Malignancies
375 mg/m^2 Intravenous on Days 1 and 8.
Other Name: Rituxan
Drug: Palifermin
60 microgram/kg by vein on Days -13 to -11 and Days 0, +1, +2
Other Name: Kepivance

  Hide Detailed Description

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 </= 1.8 mg/dL.
  4. Adequate hepatic function, as defined by SGOT and/or SGPT </= 3 x upper limit of normal; serum bilirubin and alkaline phosphatase </= 2 x upper limit of normal.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410982

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Yago Nieto, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00410982     History of Changes
Other Study ID Numbers: 2006-0803
Study First Received: December 11, 2006
Last Updated: September 24, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Neoplasms
Lymphoma
Leukemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Melphalan
Busulfan
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 18, 2014