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Autologous Stem Cell Transplants for Chronic Myelogenous Leukemia

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: NCT00446173
Recruitment Status : Withdrawn (Terminated due to low accrual.)
First Posted : March 12, 2007
Last Update Posted : August 25, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE March 9, 2007
First Posted Date  ICMJE March 12, 2007
Last Update Posted Date August 25, 2015
Study Start Date  ICMJE March 2007
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 5, 2009)
  • Time to absolute neutrophil count (ANC) recovery to 500 [ Time Frame: 30 Days ]
  • Survival Time [ Time Frame: 30 Days (Success Rate + ANC Recovery to 500) ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 9, 2007)
  • Stem cell product prior to purging:
  • Total nucleated cell count, mononuclear cell count, CD34+ cell count.
  • Quantitative PCR for BCR-ABL and cytogenetics (conventional or FISH) will be done to determine the percentage of PH+ cells.
  • Product infusion:
  • Patients will be monitored according to stem cell transplant nursing standard practices.
  • These include measurement of vital signs prior, during and post the infusion of ex-vivo culture-purged cells.
  • Patient evaluation during the first 100 days:
  • Bone marrow aspirate with cytogenetics.
  • BCR-ABL gene rearrangement in peripheral blood or bone marrow by quantitative PCR.
  • Patient evaluation after the first 100 days (every 3 months while on study:
  • Bone marrow aspirate with cytogenetics
  • BCR/ABL gene rearrangement in peripheral blood or bone marrow by quantitative PCR.
  • At each visit, a physical examination will be completed.
  • Laboratory tests to be obtained on these visits: CBC, differential, platelets, SGPT, serum bilirubin, BUN and creatinine, electrolytes.
Change History Complete list of historical versions of study NCT00446173 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Stem Cell Transplants for Chronic Myelogenous Leukemia
Official Title  ICMJE Autologous Purged Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia (CML)
Brief Summary

Primary Objective:

1. To study ex-vivo purging of autologous hematopoietic stem cells that will be used to support high-dose chemotherapy in patients with chronic myelogenous leukemia (CML). Major endpoints are neutrophil engraftment and survival.

Secondary Objectives:

  1. To evaluate the toxicity of ex-vivo purged autologous cells when used to support high-dose chemotherapy.
  2. To evaluate the rate and duration of cytogenetic remissions achieved with this strategy.
  3. To determine the time to platelet recovery to 20,000/mm3.
  4. To determine the one-year survival rate.
Detailed Description

Before treatment starts, you will have a complete physical exam. You will have about 4 tablespoons of blood drawn for tests to check on the status of the disease, to check organ functions, and to check for infectious diseases (hepatitis, HIV, etc.). You will have a sample of bone marrow collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle. You will also have heart (cardiac ejection fraction) and lung function tests. All of these tests are being done to make sure you are eligible for this treatment.

In order to access the blood in the circulation, a silicone catheter (small plastic tube) will be placed in the collar bone area. You will be under local anesthesia during this procedure. If you are found to be eligible to take part in this study, this catheter will be used for the collection of stem cells, infusion of chemotherapy, fluids, electrolytes, other medications, and also for blood sampling for lab tests. It will remain in your body for the length of the treatment (between 2-5 months).

Normally, there are very few stem cells in the blood. The majority of them are in the bone marrow. To help move or "mobilize" the cells needed from your bone marrow to your blood, you will be given chemotherapy followed by injections under the skin once a day of a drug called G-CSF and another drug called GM-CSF. These injections will be given over 7-21 days. The injections may be given by a nurse in the hospital, in the outpatient setting, or you may learn how to give them to yourself.

The chemotherapy you will receive to help mobilize the stem cells is cyclophosphamide. It will be given by vein over a few hours in one day. This is the first step toward collecting the stem cells necessary for transplantation later on. It is separate from the high-dose chemotherapy that you get after the transplant.

Blood samples (about 4 teaspoons each) will be drawn once a day after the cyclophosphamide to check for the numbers of stem cells in your blood and to monitor for possible side effects. If the number of stem cells in the blood is high enough, you will go to the UTMDACC Apheresis Unit and have your peripheral blood progenitor cells (PBPC, or stem cells) collected.

The procedure to collect your cells is called leukapheresis. It is similar to donating platelets to a blood bank. The cells will be removed from the blood through the catheter and the remaining blood will be given back to you through the catheter. This procedure is performed in a machine that processes the blood and separates the cells needed for transplantation, giving the rest back to you. Each leukapheresis procedure takes about 4-6 hours. You will have one leukapheresis procedure a day, for 1 to 5 days in a row, until enough stem cells are collected for the transplant and for ""back-up" in case of problems with the treated cells. If after 5 procedures, the number of cells collected is too low, additional collections of cells may be needed.

Some people may not be able to have enough cells collected through the blood. If this is the case, you may need to have bone marrow stem cells collected. You will be taken to the operating room and have multiple collections of bone marrow performed. The procedure will be performed while you are under general anesthesia. About 1 - 1.5 liters of bone marrow will be collected. You will be asked to donate your own blood before the procedure if possible. That blood will be given back to you in the operating room. Somebody else's blood may be given to you instead if you cannot donate.

After enough stem cells are collected, the cells will be treated in the laboratory, using Gleevec (imatinib mesylate) followed by ex vivo culture/purging. Culture-purging is a method that takes advantage of the fact that CML cells die when kept in laboratory culture in a shorter time period than normal blood cells. If the cells are kept alive long enough, surviving cells will be less contaminated by CML cells. Imatinib mesylate will provide a chemical way of killing the CML cells, since they are more toxic to CML cells than they are to normal cells. The culture-purging will also use three medications called "growth factors". The medications being used are stem cell factor, G-CSF, and thrombopoietin.

Busulfan and cyclophosphamide are chemotherapy drugs that are designed to kill leukemia cells. However, the combination will kill a significant amount of your bone marrow cells, which will basically stop the production of blood components. In order to restart the production, the cells that were removed and treated in the lab will be given back to you (autologous transplant).

You will be admitted to the hospital to receive high dose chemotherapy. You will be given busulfan by continuous injection (using the catheter) for 4 days, then you will be given cyclophosphamide by a continuous injection (using the catheter) for 2 days. You may also receive antibiotics, fluids, and other medications if your doctor feels it is necessary.

After you receive the chemotherapy, you will be given your treated bone marrow or blood stem cells back. To help speed up the recovery of white blood cells, you will also be given G-CSF by injection under the skin once a day until the white blood count has recovered (usually 2 to 3 weeks) and GM-CSF under the skin for a month. You may also receive antibiotics, fluids, and other medications if your doctor feels it is necessary. Blood tests (about 4 teaspoons) are repeated several times per week until blood counts are fully recovered and any side effects of the high dose therapy have resolved.

You will have check-up visits 1, 3, 6, and 12 months after the transplant. At these visits, you will have bone marrow samples collected to monitor the disease response. Bone marrow samples may also be collected for research at the same time points. These samples will be used to determine the survival of stem cells in laboratory conditions after the transplant. You will have blood collected (1- 4 tablespoons) for routine blood tests.

This is an investigational study. Busulfan, cyclophosphamide, G-CSF and GM-CSF are commercially available drugs. Up to 48 patients will take part in this study. All will be treated at M. D. Anderson.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia
Intervention  ICMJE
  • Drug: Busulfan
    130 mg/m^2 IV Daily Over 3 Hours x 4 Days
    Other Names:
    • Bulsulfex
    • Myleran
  • Drug: Cyclophosphamide
    60 mg/kg IV Daily Over 4 Hours x 2 Days
    Other Names:
    • Cytoxan
    • Neosar
  • Drug: G-CSF
    10 mcg/kg Subcutaneously Once Daily
    Other Names:
    • Filgrastin
    • Neupogen
  • Drug: GM-CSF
    250 mcg/kg Subcutaneously Once Daily
    Other Names:
    • Sargramostim
    • Leukine
Study Arms  ICMJE Experimental: Busulfan + Cyclophosphamide + G-CSF + GM-CSF
Interventions:
  • Drug: Busulfan
  • Drug: Cyclophosphamide
  • Drug: G-CSF
  • Drug: GM-CSF
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: May 21, 2009)
0
Original Enrollment  ICMJE
 (submitted: March 9, 2007)
48
Actual Study Completion Date  ICMJE January 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with Philadelphia (Ph) chromosome positive CML < age 65 and older than 21 years.
  • Ph positive CML that is either in: 1. late 1st chronic phase (> 2 years from diagnosis) 2. early chronic phase who did not achieve complete cytogenetic remission after one year on imatinib 3. beyond first chronic phase 4. accelerated phase 5. blastic phase that has responded to therapy (characterized by the presence of < 10% bone marrow and/or circulating blasts at consent signing) 6. chronic phase, developing imatinib resistance (loss of molecular remission defined as at least a 1 log increase in the BCR-ABL/ABL ratio, in 2 time points at least 1 month apart, or loss of cytogenetic remission)
  • Patients must have a Zubrod PS < 3. Creatinine < 1.8 mg/dl
  • Serum bilirubin </= 1.5 mg/dl
  • Serum glutamate pyruvate transaminase (SGPT) < 3 x normal values
  • Patients with an HLA identical sibling are eligible if they refuse allogeneic transplantation, or if they are ineligible for allogeneic transplantation due to age.
  • DLCO >/= 50% of predicted
  • Cardiac Ejection fraction >/= 40%

Exclusion Criteria:

  • Uncontrolled life-threatening infections or comorbid condition that could impair tolerance to the regimen.
  • HIV positivity.
  • Pregnant or lactating women.
  • CML in blastic phase that has not responded to therapy given prior to enrollment in this study (characterized by the presence of more than 9% bone marrow and/or peripheral blood blasts at the time of consent signing)
  • Hepatitis B or C virus infection. Hepatitis B infection defined by positive DNA test, positive E and / or surface antigen.
  • CML in first molecular remission.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00446173
Other Study ID Numbers  ICMJE 2003-0710
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Marcos de Lima, MD/Associate Professor, U.T.M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Marcos de Lima, MD M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP