Allogeneic Stem Cell Transplant for CLL

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT01629511
Collaborator
National Cancer Institute (NCI) (NIH)
15
1
1
65.1
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine the maximum tolerated dose (MTD) of gemcitabine when administered with busulfan and clofarabine.

  2. 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:
  1. 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 Design

Study Type:
Interventional
Actual Enrollment :
15 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Clofarabine, Gemcitabine, and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
Nov 21, 2012
Actual Primary Completion Date :
Apr 25, 2018
Actual Study Completion Date :
Apr 25, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (combination chemotherapy, stem cell transplant)

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo stem cell transplant
Other Names:
  • Allogeneic Hematopoietic Cell Transplantation
  • Allogeneic Stem Cell Transplantation
  • HSC
  • HSCT
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin
  • Drug: Busulfan
    Given IV
    Other Names:
  • 1, 4-Bis[methanesulfonoxy]butane
  • BUS
  • Bussulfam
  • Busulfanum
  • Busulfex
  • Busulphan
  • CB 2041
  • CB-2041
  • Glyzophrol
  • GT 41
  • GT-41
  • Joacamine
  • Methanesulfonic Acid Tetramethylene Ester
  • Methanesulfonic acid, tetramethylene ester
  • Mielucin
  • Misulban
  • Misulfan
  • Mitosan
  • Myeleukon
  • Myeloleukon
  • Myelosan
  • Mylecytan
  • Myleran
  • Sulfabutin
  • Tetramethylene Bis(methanesulfonate)
  • Tetramethylene bis[methanesulfonate]
  • WR-19508
  • Drug: Clofarabine
    Given IV
    Other Names:
  • Clofarex
  • Clolar
  • Biological: Filgrastim
    Given SC
    Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim
  • Drug: Gemcitabine
    Given IV
    Other Names:
  • dFdC
  • dFdCyd
  • Difluorodeoxycytidine
  • Drug: Methotrexate
    Given IV
    Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
  • Drug: Tacrolimus
    Given PO
    Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic
  • Outcome Measures

    Primary Outcome Measures

    1. 100 Day Treatment Related Mortality (TRM) [100 days post transplant]

      Number of deaths related to treatment by day 100 post allogeneic transplant

    2. Maximum Tolerated Dose (MTD) [Enrollment up to day 30 post transplant]

      To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan & Clofarabine

    Secondary Outcome Measures

    1. Overall Survival [Up to 1 year post transplant]

      Will be estimated by the method of Kaplan and Meier. Time-to-event distributions as function of patient baseline covariates will be evaluated using Bayesian time-to-event regression modeling.

    Other Outcome Measures

    1. Progression-free Survival (PFS) [Up to 1 year post transplant]

      Number of patients without any relapse post treatment completion

    2. Time-to-engraftment [30 days post transplant]

      The number of days until participants by dose level reach engraftment.

    3. Acute and Chronic Graft Verse Host Disease (GvHD) [Up to 1 year post transplant]

      GvHD (Graft versus Host Disease) occurs when immune cells transplanted from a non-identical donor (graft) recognizes the transplant recipient (the host) as foreign, thereby initiating an immune reaction in the transplant recipient. Acute GvHD typically occurs around the time of engraftment and manifests in skin, GI system, and liver abnormalities. Chronic GvHD is defined by manifestations such as ocular, oral, lung, sclerosis skin, failure to thrive, fascia, cholestasis in liver, esophagus strictures.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Chitra Hosing, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01629511
    Other Study ID Numbers:
    • 2012-0249
    • NCI-2018-01798
    • 2012-0249
    • P30CA016672
    First Posted:
    Jun 27, 2012
    Last Update Posted:
    Feb 24, 2020
    Last Verified:
    Feb 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants enrolled at MD Anderson clinic starting on November 21, 2012 on Phase I of the study. No participants were enrolled on Phase II.
    Pre-assignment Detail
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Period Title: Overall Study
    STARTED 4 0 8 3
    COMPLETED 4 0 8 3
    NOT COMPLETED 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4 Total
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Total of all reporting groups
    Overall Participants 4 0 8 3 15
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    3
    75%
    0
    NaN
    7
    87.5%
    3
    100%
    13
    86.7%
    >=65 years
    1
    25%
    0
    NaN
    1
    12.5%
    0
    0%
    2
    13.3%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    56
    57.5
    60
    59
    Sex: Female, Male (Count of Participants)
    Female
    3
    75%
    0
    NaN
    2
    25%
    0
    0%
    5
    33.3%
    Male
    1
    25%
    0
    NaN
    6
    75%
    3
    100%
    10
    66.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    1
    25%
    0
    NaN
    2
    25%
    2
    66.7%
    5
    33.3%
    Unknown or Not Reported
    3
    75%
    0
    NaN
    6
    75%
    1
    33.3%
    10
    66.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    White
    4
    100%
    0
    NaN
    8
    100%
    3
    100%
    15
    100%
    More than one race
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    4
    100%
    0
    NaN
    8
    100%
    3
    100%
    15
    100%
    Disease Category (Count of Participants)
    Diseases : Chronic Lymphocytic Leukemia (CLL)
    3
    75%
    0
    NaN
    5
    62.5%
    1
    33.3%
    9
    60%
    Diseases : Prolymphocytic Leukemia (PLL)
    1
    25%
    0
    NaN
    2
    25%
    2
    66.7%
    5
    33.3%
    Diseases: Richter's
    0
    0%
    0
    NaN
    1
    12.5%
    0
    0%
    1
    6.7%

    Outcome Measures

    1. Primary Outcome
    Title 100 Day Treatment Related Mortality (TRM)
    Description Number of deaths related to treatment by day 100 post allogeneic transplant
    Time Frame 100 days post transplant

    Outcome Measure Data

    Analysis Population Description
    No participants were treated at dose level 2.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Measure Participants 4 0 8 3
    Infection
    0
    0%
    0
    NaN
    0
    0%
    0
    0%
    Graft versus Host Disease (GVHD)
    0
    0%
    0
    NaN
    1
    12.5%
    0
    0%
    2. Primary Outcome
    Title Maximum Tolerated Dose (MTD)
    Description To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan & Clofarabine
    Time Frame Enrollment up to day 30 post transplant

    Outcome Measure Data

    Analysis Population Description
    MTD analysis was for Phase II. Data were not collected.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Measure Participants 0 0 0 0
    3. Secondary Outcome
    Title Overall Survival
    Description Will be estimated by the method of Kaplan and Meier. Time-to-event distributions as function of patient baseline covariates will be evaluated using Bayesian time-to-event regression modeling.
    Time Frame Up to 1 year post transplant

    Outcome Measure Data

    Analysis Population Description
    All participants were registered on Phase I.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Measure Participants 4 0 8 3
    Count of Participants [Participants]
    3
    75%
    0
    NaN
    4
    50%
    2
    66.7%
    4. Other Pre-specified Outcome
    Title Progression-free Survival (PFS)
    Description Number of patients without any relapse post treatment completion
    Time Frame Up to 1 year post transplant

    Outcome Measure Data

    Analysis Population Description
    Analysis was for Phase II. No analysis was done due to low accrual on Phase I.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Measure Participants 0 0 0 0
    5. Other Pre-specified Outcome
    Title Time-to-engraftment
    Description The number of days until participants by dose level reach engraftment.
    Time Frame 30 days post transplant

    Outcome Measure Data

    Analysis Population Description
    No participants were treated at dose level 2.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Measure Participants 4 0 8 3
    Day 10
    1
    25%
    2
    Infinity
    0
    0%
    Day 11
    2
    50%
    4
    Infinity
    0
    0%
    Day 12
    1
    25%
    0
    NaN
    1
    12.5%
    Day 13
    0
    0%
    1
    Infinity
    0
    0%
    Day 15
    0
    0%
    0
    NaN
    1
    12.5%
    Day 17
    0
    0%
    0
    NaN
    1
    12.5%
    <10 days - Graft Failure
    0
    0%
    1
    Infinity
    0
    0%
    6. Other Pre-specified Outcome
    Title Acute and Chronic Graft Verse Host Disease (GvHD)
    Description GvHD (Graft versus Host Disease) occurs when immune cells transplanted from a non-identical donor (graft) recognizes the transplant recipient (the host) as foreign, thereby initiating an immune reaction in the transplant recipient. Acute GvHD typically occurs around the time of engraftment and manifests in skin, GI system, and liver abnormalities. Chronic GvHD is defined by manifestations such as ocular, oral, lung, sclerosis skin, failure to thrive, fascia, cholestasis in liver, esophagus strictures.
    Time Frame Up to 1 year post transplant

    Outcome Measure Data

    Analysis Population Description
    Analysis was for Phase II. No analysis was done due to low accrual on Phase I.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    Measure Participants 0 0 0 0

    Adverse Events

    Time Frame Up to 100 Days post transplant
    Adverse Event Reporting Description At Gemcitabine Dose Level 2, there were no participants at that dose level and so the number of participants at risk for adverse events is zero.
    Arm/Group Title Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Arm/Group Description Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant
    All Cause Mortality
    Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/4 (25%) 0/0 (NaN) 1/8 (12.5%) 1/3 (33.3%)
    Serious Adverse Events
    Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/0 (NaN) 0/8 (0%) 0/3 (0%)
    Other (Not Including Serious) Adverse Events
    Gemcitabine Dose Level 1 Gemcitabine Dose Level 2 Gemcitabine Dose Level 3 Gemcitabine Dose Level 4
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/4 (100%) 0/0 (NaN) 8/8 (100%) 3/3 (100%)
    Blood and lymphatic system disorders
    Secondary Graft Failure 0/4 (0%) 0 0/0 (NaN) 0 1/8 (12.5%) 1 1/3 (33.3%) 1
    Primary Graft Failure 0/4 (0%) 0 0/0 (NaN) 0 1/8 (12.5%) 1 0/3 (0%) 0
    Cardiac disorders
    Hypertension 4/4 (100%) 4 0/0 (NaN) 0 1/8 (12.5%) 1 1/3 (33.3%) 1
    Gastrointestinal disorders
    Diarrhea 2/4 (50%) 2 0/0 (NaN) 0 4/8 (50%) 4 2/3 (66.7%) 2
    Mucositis 4/4 (100%) 4 0/0 (NaN) 0 6/8 (75%) 6 2/3 (66.7%) 2
    Nausea 3/4 (75%) 3 0/0 (NaN) 0 8/8 (100%) 8 3/3 (100%) 3
    General disorders
    Fluid Overload 4/4 (100%) 4 0/0 (NaN) 0 5/8 (62.5%) 5 3/3 (100%) 3
    Fever 4/4 (100%) 5 0/0 (NaN) 0 1/8 (12.5%) 1 2/3 (66.7%) 2
    Neutropenic Fever 3/4 (75%) 3 0/0 (NaN) 0 7/8 (87.5%) 7 2/3 (66.7%) 2
    Acute Graft versus Host Disease 3/4 (75%) 5 0/0 (NaN) 0 3/8 (37.5%) 7 2/3 (66.7%) 5
    Chronic Graft versus Host Disease 2/4 (50%) 3 0/0 (NaN) 0 3/8 (37.5%) 8 2/3 (66.7%) 8
    Hepatobiliary disorders
    Transaminitis 3/4 (75%) 5 0/0 (NaN) 0 6/8 (75%) 6 3/3 (100%) 4
    Elevated Bilirubin 3/4 (75%) 3 0/0 (NaN) 0 5/8 (62.5%) 5 1/3 (33.3%) 1
    Infections and infestations
    Infection 4/4 (100%) 8 0/0 (NaN) 0 8/8 (100%) 15 3/3 (100%) 7
    Nervous system disorders
    Headaches 0/4 (0%) 0 0/0 (NaN) 0 2/8 (25%) 2 1/3 (33.3%) 1
    Renal and urinary disorders
    Elevated Creatinine 2/4 (50%) 2 0/0 (NaN) 0 0/8 (0%) 0 1/3 (33.3%) 2
    Hemorrhagic Cystitis 1/4 (25%) 1 0/0 (NaN) 0 0/8 (0%) 0 0/3 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis 1/4 (25%) 1 0/0 (NaN) 0 1/8 (12.5%) 1 0/3 (0%) 0
    Skin and subcutaneous tissue disorders
    Skin Rash 3/4 (75%) 3 0/0 (NaN) 0 4/8 (50%) 4 1/3 (33.3%) 1

    Limitations/Caveats

    Early termination leading to small number of subjects analyzed. This study never moved to Phase II, therefore was not analyzed.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Chitra Hosing
    Organization UT MD Anderson Cancer Center
    Phone 713-792-8750
    Email cmhosing@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01629511
    Other Study ID Numbers:
    • 2012-0249
    • NCI-2018-01798
    • 2012-0249
    • P30CA016672
    First Posted:
    Jun 27, 2012
    Last Update Posted:
    Feb 24, 2020
    Last Verified:
    Feb 1, 2020