A Study of Bone Marrow Transplantation Using Fully-Matched Relatives as Donors for Patients With Hematological Malignancies
Study Details
Study Description
Brief Summary
This research study uses a drug called cyclophosphamide to decrease the incidence of GVHD in matched sibling hematopoietic stem cell transplant. In doing so, the goal of the study is to increase overall survival.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
This research protocol has been developed for patients undergoing matched-sibling hematopoietic stem cell transplant (HSCT). The patients who are treated according to this 2 step allogeneic HSCT protocol will receive cyclophosphamide to induce in-vivo tolerization of both autologous and allogeneic lymphocytes, followed by an allogeneic CD34-selected HSCT. The primary research questions relate to immune reconstitution, incidence of GVHD, and relapse in patients who receive lymphocyte treatment of this type in allogeneic HSCT and how it impacts overall survival.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Allogeneic Transplantation Matched Sibling Allogeneic Transplantation |
Device: Matched Sibling Allogeneic Transplantation
Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Patients With Overall Survival [1 Year after transplant]
The primary objective of this prospective, phase II trial was to obtain an OS rate of >60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The >60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol.
Secondary Outcome Measures
- Graft Versus Host Disease (GVHD) [1 Year after transplant]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Any patient with a hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied.
Patients will be considered high-risk if they have any of the following:
-
Age > 50 years
-
ECOG Performance status of <2
-
Acute leukemia: requiring more than one chemotherapy regimen to obtain 1st CR; second or greater CR, 1st relapse; any ph+ ALL
-
CML 2nd chronic phase, accelerated phase, or blastic phase
-
MDS with IPS of Intermediate 2 or greater
-
Any myeloproliferative disorder
-
Hodgkin lymphoma: relapsed, refractory, or primary induction failure
-
Non-Hodgkin lymphoma: relapsed, refractory, primary treatment failure, or not eligible for an autologous HSCT
-
Other conditions not listed will be assessed as high-risk by the PI
-
Patients must have a related donor who is either HLA-identical or a one antigen mismatch at the HLA- A; B; C; and DR loci.
-
Patients must adequate organ function:
-
LVEF of >45%
-
DLCO (adjusted for hemoglobin) >45% of predicted
-
Adequate liver function as defined by a serum bilirubin <1.8, AST or ALT < 2.5X upper limit of normal
-
Creatinine clearance of > 60 ml/min
-
Patients must be willing to use contraception if they have childbearing potential
-
Able to give informed consent
Exclusion Criteria:
-
ECOG performance status of 3 or 4.
-
HIV positive
-
Active involvement of the central nervous system with malignancy
-
Psychiatric disorder that would preclude patients from signing an informed consent
-
Pregnancy
-
Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Thomas Jefferson University | Philadelphia | Pennsylvania | United States | 19107 |
Sponsors and Collaborators
- Sidney Kimmel Cancer Center at Thomas Jefferson University
Investigators
- Principal Investigator: Neal Flomenberg, MD, Thomas Jefferson University
Study Documents (Full-Text)
More Information
Additional Information:
- Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
- Thomas Jefferson University Hospitals
Publications
None provided.- 08D.85
- 2007-61
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Allogeneic Transplantation |
---|---|
Arm/Group Description | Matched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization |
Period Title: Overall Study | |
STARTED | 47 |
COMPLETED | 46 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Allogeneic Transplantation |
---|---|
Arm/Group Description | Matched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization |
Overall Participants | 46 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
11
23.9%
|
>=65 years |
35
76.1%
|
Sex: Female, Male (Count of Participants) | |
Female |
16
34.8%
|
Male |
30
65.2%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
4
8.7%
|
Not Hispanic or Latino |
40
87%
|
Unknown or Not Reported |
2
4.3%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
3
6.5%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
4
8.7%
|
White |
37
80.4%
|
More than one race |
0
0%
|
Unknown or Not Reported |
2
4.3%
|
Region of Enrollment (participants) [Number] | |
United States |
46
100%
|
Outcome Measures
Title | Number of Patients With Overall Survival |
---|---|
Description | The primary objective of this prospective, phase II trial was to obtain an OS rate of >60% at 1 year in patients undergoing a 2 step HSCT from an HLA compatible family donor. The >60% threshold was selected as a composite efficacy measure as patients with any hematologic diagnosis, stage of disease, or age as old as 65 years were eligible for this treatment protocol. |
Time Frame | 1 Year after transplant |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Allogeneic Transplantation |
---|---|
Arm/Group Description | Matched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization |
Measure Participants | 46 |
Count of Participants [Participants] |
41
89.1%
|
Title | Graft Versus Host Disease (GVHD) |
---|---|
Description | |
Time Frame | 1 Year after transplant |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Allogeneic Transplantation |
---|---|
Arm/Group Description | Matched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization |
Measure Participants | 46 |
Acute GVHD |
6
13%
|
Chronic GVHD |
4
8.7%
|
No GVHD |
36
78.3%
|
Adverse Events
Time Frame | from baseline through one year after transplant | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Allogeneic Transplantation | |
Arm/Group Description | Matched Sibling Allogeneic Transplantation Matched Sibling Allogeneic Transplantation: Patients undergoing myeloablative hematopoietic stem cell transplant from HLA identical related donors using cyclophosphamide tolerization | |
All Cause Mortality |
||
Allogeneic Transplantation | ||
Affected / at Risk (%) | # Events | |
Total | 16/46 (34.8%) | |
Serious Adverse Events |
||
Allogeneic Transplantation | ||
Affected / at Risk (%) | # Events | |
Total | 0/46 (0%) | |
Other (Not Including Serious) Adverse Events |
||
Allogeneic Transplantation | ||
Affected / at Risk (%) | # Events | |
Total | 32/46 (69.6%) | |
Gastrointestinal disorders | ||
Mucositis | 32/46 (69.6%) | 32 |
Diarrhea | 30/46 (65.2%) | 35 |
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 | Neal Flomenberg, MD |
---|---|
Organization | Sidney Kimmel Cancer Center at Thomas Jefferson University |
Phone | 215-955-4367 |
Neal.Flomenberg@jefferson.edu |
- 08D.85
- 2007-61