Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia (CLL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01629511
First received: June 25, 2012
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

The goal of this clinical research study is to learn the highest tolerable dose of gemcitabine (out of 4 possible doses) that can be given in combination with busulfan and clofarabine before an allogeneic stem cell transplant. Researchers also want to learn if this combination can help to control CLL. The safety of this treatment will also be studied.

Busulfan is designed to bind to DNA (the genetic material of cells), which may cause cancer cells to die. It is commonly used in stem cell transplants.

Clofarabine and gemcitabine are designed to block the growth of cancer cells, which may cause the cancer cells to die.


Condition Intervention Phase
Leukemia
Drug: Busulfan
Drug: Clofarabine
Drug: Gemcitabine
Drug: Thymoglobulin
Procedure: Allogeneic Stem Cell Transplantation
Drug: Filgrastim
Drug: Tacrolimus
Drug: Methotrexate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clofarabine, Gemcitabine and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Gemcitabine with Busulfan and Clofarabine [ Time Frame: 30 days after allogeneic stem cell transplant ] [ Designated as safety issue: Yes ]
    Toxicity defined as any of the three events grade 4 mucositis, grade 4 skin toxicity, or death from any cause, occurring within 30 days from transplant.


Secondary Outcome Measures:
  • Success Rate [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    Success rate defined as all of three efficacy outcomes that patient is (i) alive, (ii) engrafted, and (ii) without grade 3 or 4 (i.e., severe) graft versus host disease (GVHD) at 100 days post allogeneic transplant. Overall survival (OS), progression free survival (PFS), and time-to-engraftment all are defined from day of allogeneic transplant, to day of event.


Estimated Enrollment: 30
Study Start Date: November 2012
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Busulfan + Clofarabine + Gemcitabine + Transplant

Clofarabine administered at dose of 30 mg/m2 by vein infused over 1 hour on Days -6 through -3. Busulfan test dose of 32 mg/m2 based on actual body weight given by vein over 60 minutes. Busulfan administered at dose calculated to achieve a systemic exposure dose of 4000 µMol-min in normal saline over 3 hours by vein every 24 hours on Days -6 to -3, starting immediately after the completion of Clofarabine. Gemcitabine dosing begin at 275 mg/m2/dose by vein preceded by a loading dose of 75 mg/m2 administered as a bolus: 75 mg/m2 + (10mg/m2/ min × 10 min) = 175 mg/m2 .

Patients receiving a graft from a matched unrelated donor receive Thymoglobulin; 0.5 mg/kg on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1.

Allogeneic hematopoietic cell transplantation on Day 0.

Drug: Busulfan

32 mg/m2 test dose by vein based on actual body weight given between Day -15 and Day -8.

Busulfan administered at dose calculated to achieve a systemic exposure dose of 4000 µMol-min in normal saline over 3 hours by vein every 24 hours on Days -6 to -3, starting one hour after the completion of Clofarabine.

Other Names:
  • Busulfex
  • Myleran
Drug: Clofarabine
30 mg/m2 diluted in NS to produce a final concentration of 0.4mg/mL by vein on Days -6 through -3.
Other Names:
  • Clofarex
  • Clolar
Drug: Gemcitabine

Phase I Starting Dose: 275 mg/m2 by vein preceded by a loading dose of 75 mg/m2 administered as a bolus on Days -6 and -4.

Phase II Starting Dose: Maximum tolerated dose (MTD) from Phase I.

Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar
Drug: Thymoglobulin
0.5 mg/kg by vein on Day -3, 1.5 mg/kg on Day -2 and 2.0 mg/kg on Day -1 for patients receiving a graft from a matched unrelated donor.
Other Names:
  • ATG
  • Antithymocyte Globulin
Procedure: Allogeneic Stem Cell Transplantation
Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.
Drug: Filgrastim
5 mcg/kg subcutaneously 1 time each day starting 1 week after the transplant until blood cell levels return to normal.
Other Names:
  • G-CSF
  • Neupogen
Drug: Tacrolimus
Starting dose of 0.015 mg/kg by vein as a 24 hour continuous infusion daily beginning on Day -2, adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no GVHD is present.
Other Name: Prograf
Drug: Methotrexate
5 mg/m2 by vein on Days +1, +3, +6 and +11 post transplant.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 to 70 years of age.
  2. 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.
  3. A 10/10 HLA matched (high resolution typing at A, B, C, DRB1, DQ1) sibling or unrelated donor.
  4. Left ventricular EF > 40%.
  5. FEV1, FVC and corrected DLCO > 40%.
  6. Serum creatinine < 1.6 mg/dL. Serum bilirubin < 2X upper limit of normal.
  7. SGPT < 2X upper limit of normal.
  8. Voluntary signed, written IRB-approved informed consent.
  9. 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:

  1. Patient with active CNS disease.
  2. Pregnant (Positive Beta 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.
  3. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
  4. Active uncontrolled bacterial, viral or fungal infections.
  5. Patient has received other investigational drugs within 2 weeks before enrollment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01629511

Contacts
Contact: Chitra M. Hosing, MD 713-792-8750

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Chitra M. Hosing, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01629511     History of Changes
Other Study ID Numbers: 2012-0249, NCI-2012-01248
Study First Received: June 25, 2012
Last Updated: September 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Chronic lymphocytic leukemia
CLL
Allogeneic hematopoietic cell transplantation\
HCT
Methotrexate
Filgrastim
G-CSF
Neupogen
Tacrolimus
Prograf
Busulfan
Busulfex
Myleran
Clofarabine
Clofarex
Clolar
Gemcitabine
Gemcitabine Hydrochloride
Gemzar
Thymoglobulin
ATG
Antithymocyte Globulin

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Gemcitabine
Methotrexate
Clofarabine
Tacrolimus
Busulfan
Antilymphocyte Serum
Lenograstim
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on October 16, 2014