Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00990249

Recruitment Status : Completed

First Posted : October 6, 2009

Results First Posted : August 7, 2018

Last Update Posted : August 7, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

M.D. Anderson Cancer Center

Study Description

Brief Summary:

The goal of this clinical research study is to test the safety of giving clofarabine in combination with busulfan, followed by an allogeneic (from a donor) stem cell transplant, in patients with advanced leukemia or lymphoma.

Condition or disease	Intervention/treatment	Phase
Leukemia Lymphoma Allogeneic Haematopoietic Stem Cell Transplantation Acute Lymphoblastic Leukemia	Drug: Busulfan Drug: Clofarabine Drug: Thymoglobulin Procedure: Stem Cell Transplant	Phase 2

Show detailed description

Detailed Description:

Study Treatment:

Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants.

Clofarabine is designed to interfere with the growth and development of cancer cells.

A stem cell transplant is designed to help your body attack the cancer cells that may remain in your body after chemotherapy.

Central Venous Catheter Placement:

If you are found to be eligible to take part in this study, you will have a central venous catheter (CVC) placed. 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 this procedure to you in more detail, and you will be required to sign a separate consent form for it.

The study drugs and stem cells will be given by vein through your CVC. The CVC will remain in your body for about 3 months.

Study Drug Administration and Stem Cell Transplant:

You will first receive a low-level "test" dose of busulfan by vein, either over 45 or 60 minutes, on Day -8 (8 days before the transplant).

A heparin lock will be placed in your vein to lower the number of needle sticks needed for the blood draws. This will involve placing an intravenous (IV) line in your lower arm that will remain in place from Day -8 through Day -6.

Blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing up to 11 times over the 11 hours after the busulfan dose on Day -8. PK testing measures the amount of study drug in the body at different time points. This PK testing will be done to find the dose of busulfan needed for your body size on the other days that you receive busulfan.

Each day from Day -6 through Day -3, you will receive clofarabine by vein over 1 hour and your body-specific dose of busulfan by vein over 3 hours. If for any reason you could not have the PK tests performed, you will receive the standard busulfan dose on these days.

The PK testing will be repeated on Day -6. Blood (about 1 teaspoon each time) will be drawn for PK testing up to 11 times over the 11 hours after the busulfan dose.

If your donor is not related to you or his/her tissue is not HLA-matched (genetically matched), you will receive antithymocyte globulin (ATG) by vein over 4 hours each day on Day -3 through Day -1. ATG is designed to weaken your immune system in order to lower the risk that your body will reject the transplant.

On Day 0, you will receive the donor's bone marrow or blood stem cells by vein. The infusion will last anywhere from about 30 minutes to several hours.

You will also receive tacrolimus and methotrexate to weaken the immune system and lower the risk of graft-versus-host disease (GVHD). GVHD is a reaction of the donor's immune cells against the recipient's body.

Tacrolimus will be given by vein over 24 hours every day, starting on Day -2 and continuing until you are able to take tacrolimus by mouth. Once you can take tacrolimus by mouth, you will take it every day for about 6 months. If you develop GVHD, the doctor may decide you need to take tacrolimus longer than 6 months.
Methotrexate will be given by vein over 15 minutes on Days 1, 3, 6, and 11 after the transplant.

Starting 1 week after the transplant, you will receive filgrastim (G-CSF) as an injection under the skin once a day until your blood cell levels return to normal.

Other Possible Treatments:

If you have a history of leukemia or lymphoma in the brain, you will receive spinal taps and chemotherapy several times over the 12 months after the transplant. The chemotherapy drug will be infused over a few minutes, during the spinal tap, directly into the space around the spinal cord. Based on standard care, the doctor will decide how often this occurs and which chemotherapy drug will be used (either methotrexate or cytarabine).

If you have a certain type of leukemia (Philadelphia chromosome positive acute lymphoblastic leukemia [ALL]), you will receive an additional drug to help prevent the cancer from returning. The drug will be imatinib mesylate or another similar type of drug that the doctor decides. It will be given by mouth, every day for up to 1 year after the transplant.

Length of Study Participation:

You will be in the hospital for about 4 weeks after the transplant. You will be taken off study if the disease gets worse. The study drugs will be stopped if intolerable side effects occur.

Follow-Up:

At 1, 3, 6, and 12 months after the transplant, the following tests and procedures will be performed:

Blood (about 4 tablespoons) will be drawn for routine tests.
You will have a bone marrow aspiration to check the status of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
If the disease was not in your bone marrow at the time of diagnosis, you will have a CT and/or positron emission computed tomography (PET) scan to check the status of the disease.

The study staff will stay in contact with your local doctor to find out if the leukemia or lymphoma comes back, as well as to check how you are doing.

This is an investigational study. Busulfan and clofarabine are commercially available and FDA approved for the treatment of cancer. Busulfan is also FDA approved for use with stem cell transplants. The use of these drugs together with a stem cell transplant is investigational.

Up to 150 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	120 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Busulfan Plus Clofarabine Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Acute Lymphoblastic Leukemia or Lymphoma, or Biphenotypic Leukemia
Study Start Date :	October 2009
Actual Primary Completion Date :	May 2016
Actual Study Completion Date :	May 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia Lymphoma

Drug Information available for: Busulfan Clofarabine

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Acute Graft Versus Host Disease Acute Leukemia of Ambiguous Lineage

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Busulfan + Clofarabine + Stem Cell Transplant Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose. Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors. Stem cell infusion on Day 0.	Drug: Busulfan Test Dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose. Other Names: Busulfex Myleran Drug: Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3 Other Names: Clolar Clofarex Drug: Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors Other Names: Anti-thymocyte globulin ATG Procedure: Stem Cell Transplant Stem cell infusion on Day 0. Other Names: Allogeneic hematopoietic cell transplant HCT

Arm

Intervention/treatment

Experimental: Busulfan + Clofarabine + Stem Cell Transplant

Busulfan test dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.

Clofarabine 40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3. Thymoglobulin 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors.

Stem cell infusion on Day 0.

Drug: Busulfan

Test Dose 32 mg/m^2 by vein over 45 minutes on Day -8; following doses on Days -6 to -3 derived from pharmacokinetic (PK) testing done up to 11 times over 11 hours after test dose.

Other Names:

Busulfex
Myleran

Drug: Clofarabine

40 mg/m^2 by vein over 1 hour daily Day -6 through Day -3

Other Names:

Clolar
Clofarex

Drug: Thymoglobulin

0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1; only patients with HLA nonidentical or unrelated donors

Other Names:

Anti-thymocyte globulin
ATG

Procedure: Stem Cell Transplant

Stem cell infusion on Day 0.

Other Names:

Allogeneic hematopoietic cell transplant
HCT

Outcome Measures

Primary Outcome Measures :

Treatment-Related Mortality (TRM) Defined as Non Relapse Mortality (NRM) [ Time Frame: 100 Days ]
NRM was defined as death from any cause other than disease progression or relapse and reported as percentage of participant deaths. Treatment related deaths after transplant are defined either by deaths which could not be attributed to disease relapse or progression or by deaths without previous relapse or progression. For TRM at day 100, Bayesian method of Thall, Simon, and Estey used to perform interim monitoring.

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	up to 65 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with biopsy-proven acute lymphoblastic leukemia, acute lymphoblastic lymphoma, or acute biphenotypic leukemia in remission or relapse.
Adequate renal function, as defined by estimated serum creatinine clearance >60 ml/min.
Bilirubin equal or less than 1.5 (unless Gilbert's Syndrome), serum glutamate pyruvate transaminase (SGPT) <3 X upper limit of normal and alkaline phosphatase <2 X upper limit of normal.
Adequate pulmonary function with forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusion capacity of lung for carbon monoxide (DLCO) at least 45% of expected corrected for hemoglobin. Children unable to perform pulmonary functions must have an oxygen saturation greater than 92% at room air.
Adequate cardiac function with left ventricular ejection fraction at least 45% on appropriate medical therapy. No uncontrolled arrhythmias or symptomatic cardiac disease.
Zubrod performance status <2 or Lansky/Karnofsky PS equal or greater to 70%.
Patients must have a related, genotypically HLA identical donor, or they must have a unrelated donor who is 8/8 HLA match by high resolution typing.
Patient or patient's legal representative, parent(s) or guardian should provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
Negative Beta Human Chorionic Gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months and no previous surgical sterilization.

Exclusion Criteria:

Patients with unresolved grade >2 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.
Uncontrolled infection, including HIV, HTLV-1, hepatitis B or hepatitis C viremia.
Patients greater than 65 years-old.
Prior autologous or allogeneic hematopoietic stem cell transplant.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00990249

Locations

Layout table for location information

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Layout table for investigator information

Study Chair:	Partow Kebriaei, MD	M.D. Anderson Cancer Center

More Information

Additional Information:

University of Texas MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

Layout table for additonal information

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00990249
Other Study ID Numbers:	2009-0209 NCI-2012-01270 ( Registry Identifier: NCI CTRP )
First Posted:	October 6, 2009 Key Record Dates
Results First Posted:	August 7, 2018
Last Update Posted:	August 7, 2018
Last Verified:	May 2017

Keywords provided by M.D. Anderson Cancer Center:


Acute Lymphoblastic Leukemia ALL Acute lymphoblastic lymphoma acute biphenotypic leukemia Allogeneic hematopoietic cell transplantation HCT Stem Cell Transplant Treatment-related mortality Tyrosine kinase inhibitors	TKI Busulfan Busulfex Myleran Clofarabine Clolar Clofarex Gleevec Imatinib Mesylate

Additional relevant MeSH terms:

Layout table for MeSH terms

Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Busulfan Clofarabine	Thymoglobulin Antilymphocyte Serum Alkylating Agents Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Alkylating Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites

To Top