Allogeneic Stem Cell Transplant for CLL

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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