Allogeneic Stem Cell Transplant for CLL
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To determine the maximum tolerated dose (MTD) of gemcitabine when administered with busulfan and clofarabine.
-
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:
- 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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (combination chemotherapy, stem cell transplant) 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. |
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo stem cell transplant
Other Names:
Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
Drug: Busulfan
Given IV
Other Names:
Drug: Clofarabine
Given IV
Other Names:
Biological: Filgrastim
Given SC
Other Names:
Drug: Gemcitabine
Given IV
Other Names:
Drug: Methotrexate
Given IV
Other Names:
Drug: Tacrolimus
Given PO
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 100 Day Treatment Related Mortality (TRM) [100 days post transplant]
Number of deaths related to treatment by day 100 post allogeneic transplant
- Maximum Tolerated Dose (MTD) [Enrollment up to day 30 post transplant]
To find the maximum tolerated dose (MTD) of Gemcitabine when administered with Busulfan & Clofarabine
Secondary Outcome Measures
- Overall Survival [Up to 1 year post transplant]
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.
Other Outcome Measures
- Progression-free Survival (PFS) [Up to 1 year post transplant]
Number of patients without any relapse post treatment completion
- Time-to-engraftment [30 days post transplant]
The number of days until participants by dose level reach engraftment.
- Acute and Chronic Graft Verse Host Disease (GvHD) [Up to 1 year post transplant]
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.
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Chitra Hosing, M.D. Anderson Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 2012-0249
- NCI-2018-01798
- 2012-0249
- P30CA016672
Study Results
Participant Flow
Recruitment Details | Participants enrolled at MD Anderson clinic starting on November 21, 2012 on Phase I of the study. No participants were enrolled on Phase II. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Period Title: Overall Study | ||||
STARTED | 4 | 0 | 8 | 3 |
COMPLETED | 4 | 0 | 8 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 | Total |
---|---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Total of all reporting groups |
Overall Participants | 4 | 0 | 8 | 3 | 15 |
Age (Count of Participants) | |||||
<=18 years |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
3
75%
|
0
NaN
|
7
87.5%
|
3
100%
|
13
86.7%
|
>=65 years |
1
25%
|
0
NaN
|
1
12.5%
|
0
0%
|
2
13.3%
|
Age (years) [Median (Full Range) ] | |||||
Median (Full Range) [years] |
56
|
57.5
|
60
|
59
|
|
Sex: Female, Male (Count of Participants) | |||||
Female |
3
75%
|
0
NaN
|
2
25%
|
0
0%
|
5
33.3%
|
Male |
1
25%
|
0
NaN
|
6
75%
|
3
100%
|
10
66.7%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||||
Hispanic or Latino |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Not Hispanic or Latino |
1
25%
|
0
NaN
|
2
25%
|
2
66.7%
|
5
33.3%
|
Unknown or Not Reported |
3
75%
|
0
NaN
|
6
75%
|
1
33.3%
|
10
66.7%
|
Race (NIH/OMB) (Count of Participants) | |||||
American Indian or Alaska Native |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
White |
4
100%
|
0
NaN
|
8
100%
|
3
100%
|
15
100%
|
More than one race |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (Count of Participants) | |||||
United States |
4
100%
|
0
NaN
|
8
100%
|
3
100%
|
15
100%
|
Disease Category (Count of Participants) | |||||
Diseases : Chronic Lymphocytic Leukemia (CLL) |
3
75%
|
0
NaN
|
5
62.5%
|
1
33.3%
|
9
60%
|
Diseases : Prolymphocytic Leukemia (PLL) |
1
25%
|
0
NaN
|
2
25%
|
2
66.7%
|
5
33.3%
|
Diseases: Richter's |
0
0%
|
0
NaN
|
1
12.5%
|
0
0%
|
1
6.7%
|
Outcome Measures
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 |
Outcome Measure Data
Analysis Population Description |
---|
No participants were treated at dose level 2. |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Measure Participants | 4 | 0 | 8 | 3 |
Infection |
0
0%
|
0
NaN
|
0
0%
|
0
0%
|
Graft versus Host Disease (GVHD) |
0
0%
|
0
NaN
|
1
12.5%
|
0
0%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
MTD analysis was for Phase II. Data were not collected. |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Measure Participants | 0 | 0 | 0 | 0 |
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 |
Outcome Measure Data
Analysis Population Description |
---|
All participants were registered on Phase I. |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Measure Participants | 4 | 0 | 8 | 3 |
Count of Participants [Participants] |
3
75%
|
0
NaN
|
4
50%
|
2
66.7%
|
Title | Progression-free Survival (PFS) |
---|---|
Description | Number of patients without any relapse post treatment completion |
Time Frame | Up to 1 year post transplant |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was for Phase II. No analysis was done due to low accrual on Phase I. |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Measure Participants | 0 | 0 | 0 | 0 |
Title | Time-to-engraftment |
---|---|
Description | The number of days until participants by dose level reach engraftment. |
Time Frame | 30 days post transplant |
Outcome Measure Data
Analysis Population Description |
---|
No participants were treated at dose level 2. |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Measure Participants | 4 | 0 | 8 | 3 |
Day 10 |
1
25%
|
2
Infinity
|
0
0%
|
|
Day 11 |
2
50%
|
4
Infinity
|
0
0%
|
|
Day 12 |
1
25%
|
0
NaN
|
1
12.5%
|
|
Day 13 |
0
0%
|
1
Infinity
|
0
0%
|
|
Day 15 |
0
0%
|
0
NaN
|
1
12.5%
|
|
Day 17 |
0
0%
|
0
NaN
|
1
12.5%
|
|
<10 days - Graft Failure |
0
0%
|
1
Infinity
|
0
0%
|
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 |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was for Phase II. No analysis was done due to low accrual on Phase I. |
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 |
---|---|---|---|---|
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant |
Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
Time Frame | Up to 100 Days post transplant | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | At Gemcitabine Dose Level 2, there were no participants at that dose level and so the number of participants at risk for adverse events is zero. | |||||||
Arm/Group Title | Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 | ||||
Arm/Group Description | Gemcitabine 100 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 150 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 200 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | Gemcitabine 250 mg/m2 IV preceded by loading dose of 75 mg/m2 for 2 days + Busulfan(adjusted Pharmacokinetic dosing) IV for 4 days + Clofarabine 30 mg/m2 IV for 4 days + Thymoglobulin 4mg/kg(Matched Unrelated Donor patients only) IV for 3 days + Stem Cell Transplant | ||||
All Cause Mortality |
||||||||
Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/4 (25%) | 0/0 (NaN) | 1/8 (12.5%) | 1/3 (33.3%) | ||||
Serious Adverse Events |
||||||||
Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/4 (0%) | 0/0 (NaN) | 0/8 (0%) | 0/3 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Gemcitabine Dose Level 1 | Gemcitabine Dose Level 2 | Gemcitabine Dose Level 3 | Gemcitabine Dose Level 4 | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/4 (100%) | 0/0 (NaN) | 8/8 (100%) | 3/3 (100%) | ||||
Blood and lymphatic system disorders | ||||||||
Secondary Graft Failure | 0/4 (0%) | 0 | 0/0 (NaN) | 0 | 1/8 (12.5%) | 1 | 1/3 (33.3%) | 1 |
Primary Graft Failure | 0/4 (0%) | 0 | 0/0 (NaN) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 |
Cardiac disorders | ||||||||
Hypertension | 4/4 (100%) | 4 | 0/0 (NaN) | 0 | 1/8 (12.5%) | 1 | 1/3 (33.3%) | 1 |
Gastrointestinal disorders | ||||||||
Diarrhea | 2/4 (50%) | 2 | 0/0 (NaN) | 0 | 4/8 (50%) | 4 | 2/3 (66.7%) | 2 |
Mucositis | 4/4 (100%) | 4 | 0/0 (NaN) | 0 | 6/8 (75%) | 6 | 2/3 (66.7%) | 2 |
Nausea | 3/4 (75%) | 3 | 0/0 (NaN) | 0 | 8/8 (100%) | 8 | 3/3 (100%) | 3 |
General disorders | ||||||||
Fluid Overload | 4/4 (100%) | 4 | 0/0 (NaN) | 0 | 5/8 (62.5%) | 5 | 3/3 (100%) | 3 |
Fever | 4/4 (100%) | 5 | 0/0 (NaN) | 0 | 1/8 (12.5%) | 1 | 2/3 (66.7%) | 2 |
Neutropenic Fever | 3/4 (75%) | 3 | 0/0 (NaN) | 0 | 7/8 (87.5%) | 7 | 2/3 (66.7%) | 2 |
Acute Graft versus Host Disease | 3/4 (75%) | 5 | 0/0 (NaN) | 0 | 3/8 (37.5%) | 7 | 2/3 (66.7%) | 5 |
Chronic Graft versus Host Disease | 2/4 (50%) | 3 | 0/0 (NaN) | 0 | 3/8 (37.5%) | 8 | 2/3 (66.7%) | 8 |
Hepatobiliary disorders | ||||||||
Transaminitis | 3/4 (75%) | 5 | 0/0 (NaN) | 0 | 6/8 (75%) | 6 | 3/3 (100%) | 4 |
Elevated Bilirubin | 3/4 (75%) | 3 | 0/0 (NaN) | 0 | 5/8 (62.5%) | 5 | 1/3 (33.3%) | 1 |
Infections and infestations | ||||||||
Infection | 4/4 (100%) | 8 | 0/0 (NaN) | 0 | 8/8 (100%) | 15 | 3/3 (100%) | 7 |
Nervous system disorders | ||||||||
Headaches | 0/4 (0%) | 0 | 0/0 (NaN) | 0 | 2/8 (25%) | 2 | 1/3 (33.3%) | 1 |
Renal and urinary disorders | ||||||||
Elevated Creatinine | 2/4 (50%) | 2 | 0/0 (NaN) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 2 |
Hemorrhagic Cystitis | 1/4 (25%) | 1 | 0/0 (NaN) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||
Pneumonitis | 1/4 (25%) | 1 | 0/0 (NaN) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||
Skin Rash | 3/4 (75%) | 3 | 0/0 (NaN) | 0 | 4/8 (50%) | 4 | 1/3 (33.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Chitra Hosing |
---|---|
Organization | UT MD Anderson Cancer Center |
Phone | 713-792-8750 |
cmhosing@mdanderson.org |
- 2012-0249
- NCI-2018-01798
- 2012-0249
- P30CA016672