Allogeneic Stem Cell Transplant for Chronic Lymphocytic Leukemia (CLL) - Full Text View

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:

MedlinePlus related topics: Cancer Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Busulfan Methotrexate Methotrexate sodium Gemcitabine Tacrolimus Filgrastim Gemcitabine hydrochloride Clofarabine Lenograstim Granulocyte colony-stimulating factor Antilymphocyte Serum

U.S. FDA Resources

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

Primary Outcome Measures:

Maximum Tolerated Dose (MTD) [ 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 175 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: 175 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.

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 175 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: 175 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:

Age 18 to 70 years of age.
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 EF > 40%.
FEV1, FVC and corrected DLCO > 40%.
Serum creatinine < 1.6 mg/dL. Serum bilirubin < 2X upper limit of normal.
SGPT < 2X upper limit of normal.
Voluntary signed, written 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 CNS disease.
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.
Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
Active uncontrolled bacterial, viral or fungal infections.
Patient has received other investigational drugs within 2 weeks before enrollment.

Contacts and Locations

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

Contacts

Contact: Chitra M. Hosing, MD

713-792-8750

Locations

United States, Texas
UT 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

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT01629511 History of Changes
Other Study ID Numbers:	2012-0249
Study First Received:	June 25, 2012
Last Updated:	April 23, 2013
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
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antilymphocyte Serum
Busulfan
Methotrexate
Gemcitabine
Tacrolimus

Lenograstim
Clofarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 23, 2013