Allogeneic Stem Cell Transplant for CLL

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Clofarabine, Gemcitabine, and Busulfan Followed by Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia (CLL)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01629511
• Other study ID #: 2012-0249
• Secondary ID: NCI-2018-0179820
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 21, 2012
• Est. completion date: April 25, 2018

Study information

• Verified date: February 2020
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: April 25, 2018
• Est. primary completion date: April 25, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Allogeneic Hematopoietic Stem Cell Transplantation Recipient
• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Prolymphocytic
• Prolymphocytic Leukemia
• Richter Syndrome

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo stem cell transplant

Biological:
• Anti-Thymocyte Globulin
Given IV

Drug:
• Busulfan
Given IV
• Clofarabine
Given IV

Biological:
• Filgrastim
Given SC

Drug:
• Gemcitabine
Given IV
• Methotrexate
Given IV
• Tacrolimus
Given PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-free Survival (PFS)	Number of patients without any relapse post treatment completion	Up to 1 year post transplant
Other	Time-to-engraftment	The number of days until participants by dose level reach engraftment.	30 days post transplant
Other	Acute and Chronic Graft Verse Host Disease (GvHD)	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.	Up to 1 year post transplant
Primary	100 Day Treatment Related Mortality (TRM)	Number of deaths related to treatment by day 100 post allogeneic transplant	100 days post transplant
Primary	Maximum Tolerated Dose (MTD)	To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan & Clofarabine	Enrollment up to day 30 post transplant
Secondary	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.	Up to 1 year post transplant

External Links

•   MD Anderson Cancer Center Website