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Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia (CLL)

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ClinicalTrials.gov Identifier: NCT01629511
Recruitment Status : Recruiting
First Posted : June 27, 2012
Last Update Posted : May 31, 2017
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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 or disease Intervention/treatment 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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group 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 : November 2012
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) of Gemcitabine with Busulfan and Clofarabine [ Time Frame: 30 days after allogeneic stem cell transplant ]
    Optimal dose of Gemcitabine determined from four doses {100, 150, 200, 250} mg/m^2 administered on days -6 and -4, using Bayesian-model-averaging continual reassessment method. For phase I dose-finding, toxicity defined as any grade 3/> non-hematologic toxicity, non-infectious toxicity or death attributable to Gemcitabine/Clofarabine/Busulfan/ATG, as well as grade 3 mucositis and grade 3 skin toxicity lasting for more than 3 days at their peak severity (i.e., grade 3), occurring within 30 days from transplant. Consideration of DLT will exclude neutropenic fever and asymptomatic, self-limited elevation of the transaminases as well as laboratory serum metabolic values not reflecting end-organ function within 30 days from transplant. Severity of the adverse events (AEs) graded according to Common Terminology Criteria v3.0 (CTCAE).

Secondary Outcome Measures :
  1. 100-Day Success Rate [ Time Frame: 100 days measured from day of allogeneic transplant. ]
    100-Day Success rate is 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 1 week before enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01629511

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

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: MD Anderson Cancer Center    877-632-6789      
Sponsors and Collaborators
M.D. Anderson Cancer Center
Principal Investigator: Chitra M. Hosing, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01629511     History of Changes
Other Study ID Numbers: 2012-0249
NCI-2012-01248 ( Registry Identifier: NCI CTRP )
First Posted: June 27, 2012    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Chronic lymphocytic leukemia
Allogeneic hematopoietic cell transplantation
Gemcitabine Hydrochloride
Antithymocyte Globulin

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antilymphocyte Serum
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents