Brief Title
Allogeneic Stem Cell Transplant for CLL
Official Title
Clofarabine, Gemcitabine, and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)
Brief Summary
This phase I/II trial studies the best dose and side effects of gemcitabine and how well it
works with clofarabine and busulfan and donor stem cell transplant in treating participants
with chronic lymphocytic leukemia. Drugs used in chemotherapy, such as gemcitabine,
clofarabine, and busulfan, work in different ways to stop the growth of tumor cells, either
by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the
bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the
healthy stem cells from a donor are infused into the patient they may help the patient's bone
marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem
cells may also replace the patient's immune cells and help destroy any remaining cancer
cells.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of gemcitabine when administered with
busulfan and clofarabine.
II. To estimate the day 100 treatment-related mortality (TRM) for the preparative regimen
busulfan, clofarabine, and gemcitabine followed by allogeneic hematopoietic cell
transplantation (HCT) for patients with chronic lymphocytic leukemia (CLL).
SECONDARY OBJECTIVES:
I. To determine the rate of progression-free survival (PFS), graft versus host disease
(GVHD), engraftment, and overall survival (OS) for this treatment regimen at one year post
treatment completion.
OUTLINE: This is a dose-escalation study of gemcitabine.
Participants receive gemcitabine intravenously (IV) over 10-25 minutes on days -6 and -4,
clofarabine IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Participants with
matched unrelated donors also receive anti-thymocyte globulin IV over 4 hours on days -3 to
-1. Starting day -2, participants receive tacrolimus orally (PO) daily for up to 6 months.
Participants undergo hematopoietic allogeneic stem cell transplant on day 0, then receive
methotrexate IV over 15 minutes on days 1, 3, 6 and 11, and filgrastim subcutaneously (SC)
once daily (QD) beginning 1 week after transplant until blood cell levels return to normal.
After completion of study treatment, participants are followed up at 3, 6 and 12 months, then
every 6 months for 1 year.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
100 Day Treatment Related Mortality (TRM)
Secondary Outcome
Overall Survival
Condition
Allogeneic Hematopoietic Stem Cell Transplantation Recipient
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Study Arms / Comparison Groups
Treatment (combination chemotherapy, stem cell transplant)
Description: Participants receive gemcitabine IV over 10-25 minutes on days -6 and -4, clofarabine IV over 1 hour and busulfan IV over 3 hours on days -6 to -3. Participants with matched unrelated donors also receive anti-thymocyte globulin IV over 4 hours on days -3 to -1. Starting day -2, participants receive tacrolimus PO daily for up to 6 months. Participants undergo hematopoietic allogeneic stem cell transplant on day 0, then receive methotrexate IV over 15 minutes on days 1, 3, 6 and 11, and filgrastim SC QD beginning 1 week after transplant until blood cell levels return to normal.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
15
Start Date
November 21, 2012
Completion Date
April 25, 2018
Primary Completion Date
April 25, 2018
Eligibility Criteria
Inclusion Criteria:
- Patients with chronic lymphocytic leukemia, prolymphocytic leukemia, or Richter's
transformation who are eligible for allogeneic transplantation and are not eligible
for protocols of higher priority
- A 10/10 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or
unrelated donor
- Left ventricular ejection fraction (EF) > 40%
- Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and corrected
diffusion capacity of the lung for carbon monoxide (DLCO) > 40%
- Serum creatinine < 1.6 mg/dL
- Serum bilirubin < 2 X upper limit of normal
- serum glutamate pyruvate transaminase (SGPT) < 2X upper limit of normal
- Voluntary signed, written Institutional Review Board (IRB)-approved informed consent
- Men and women of reproductive potential must agree to follow accepted birth control
methods for the duration of the study. Female subject is either post-menopausal or
surgically sterilized or willing to use an acceptable method of birth control (i.e., a
hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with
spermicide, or abstinence) for the duration of the study. Male subject agrees to use
an acceptable method for contraception for the duration of the study
Exclusion Criteria:
- Patient with active central nervous system (CNS) disease
- Pregnant (positive beta human chorionic gonadotropin [HCG] test in a woman with child
bearing potential defined as not post-menopausal for 12 months or no previous surgical
sterilization) or currently breast-feeding. Pregnancy testing is not required for
post-menopausal or surgically sterilized women
- Known infection with human immunodeficiency virus (HIV), human T-lymphotropic virus
(HTLV)-I, hepatitis B, or hepatitis C
- Active uncontrolled bacterial, viral or fungal infections
- Patient has received other investigational drugs within 1 week before enrollment
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Chitra Hosing, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01629511
Organization ID
2012-0249
Secondary IDs
NCI-2018-01798
Responsible Party
Sponsor
Study Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Chitra Hosing, Principal Investigator, M.D. Anderson Cancer Center
Verification Date
February 2020