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Allogeneic Stem Cell Transplant for CLL

Primary Purpose

Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Anti-Thymocyte Globulin
Busulfan
Clofarabine
Filgrastim
Gemcitabine
Methotrexate
Tacrolimus
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Allogeneic Hematopoietic Stem Cell Transplantation Recipient

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (combination chemotherapy, stem cell transplant)

Arm 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.

Outcomes

Primary Outcome Measures

100 Day Treatment Related Mortality (TRM)
Number of deaths related to treatment by day 100 post allogeneic transplant
Maximum Tolerated Dose (MTD)
To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan & Clofarabine

Secondary Outcome Measures

Overall Survival
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.

Full Information

First Posted
June 25, 2012
Last Updated
February 10, 2020
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01629511
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Terminated
Study Start Date
November 21, 2012 (Actual)
Primary Completion Date
April 25, 2018 (Actual)
Study Completion Date
April 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Richter Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (combination chemotherapy, stem cell transplant)
Arm Type
Experimental
Arm 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.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT
Intervention Description
Undergo stem cell transplant
Intervention Type
Biological
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Clofarabine
Other Intervention Name(s)
Clofarex, Clolar
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
FILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
dFdC, dFdCyd, Difluorodeoxycytidine
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Given PO
Primary Outcome Measure Information:
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
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
Secondary Outcome Measure Information:
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
Other Pre-specified Outcome Measures:
Title
Progression-free Survival (PFS)
Description
Number of patients without any relapse post treatment completion
Time Frame
Up to 1 year post transplant
Title
Time-to-engraftment
Description
The number of days until participants by dose level reach engraftment.
Time Frame
30 days post transplant
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chitra Hosing
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website

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Allogeneic Stem Cell Transplant for CLL

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