A Randomized Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation Versus Pentostatin and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies
18 Years
75 Years
Both
Hematologic Malignancies
Trial Information
A Randomized Trial of Extracorporeal Photopheresis, Pentostatin, and Total Body Irradiation Versus Pentostatin and Total Body Irradiation in Patients Undergoing Reduced Intensity Allogeneic Stem Cell Transplantation for the Treatment of Malignancies
One of the complications of allogeneic stem cell transplant (ASCT) is graft versus host
disease (GVHD). This is when the donor cells that are infused attack the body organs. This
can cause serious illness and even death. The chance of getting serious life threatening
GVHD with conventional transplant conditioning regimens is 25-50% depending on whether the
donor bone marrow is from a family member or an unrelated person. The reduced intensity
conditioning regimen used in this study involves a drug called pentostatin as well as a
reduced dose of radiation and a treatment called photopheresis. This regimen has been
successfully used in 106 patients. The incidence of serious GVHD in those patients was much
less than expected: 8% for patients getting bone marrow from a family member and 23% for
those getting bone marrow from an unrelated person. The pentostatin and radiation parts of
this reduced intensity conditioning regimen are similar to other types of reduced intensity
regimens, which use drugs similar to pentostatin. The unique part of this regimen compared
to others is the use of extracorporeal photopheresis (ECP).
While ECP has been used in 106 patients as part of a reduced intensity conditioning regimen,
it is unknown whether adding ECP to pentostatin and radiation is what caused the reduced
rate of GVHD that was seen in the previous study that was done. The use of ECP as part of a
conditioning regimen is investigational. ECP is approved by the U.S. Food and Drug
Administration (FDA) for the treatment of cutaneous T-cell lymphoma, but is not approved by
the FDA for use prior to ASCT.
Because it is not known whether the use of ECP in the reduced intensity conditioning regimen
was what caused the low incidence of GVHD, this research study will look at differences in
getting GVHD based on whether you receive ECP. Half the patients in this research study will
receive ECP as part of their reduced intensity-conditioning regimen and the other half will
not. Patients will be randomized (50% chance you will receive ECP and 50% chance you will
not). Both groups will receive pentostatin and reduced dose total body irradiation. The
primary purpose of this research study is to look at the chance of developing serious GVHD
within the first 100 days after transplant within each group.
Inclusion Criteria:
- Patients must give informed consent to receive study treatment.
- Availability of a suitable 5/6 (Class I mismatch) or 6/6 HLA-matched related or 10 or
10 matched unrelated donor.
- Adequate cardiac function with an ejection fraction ≥ 35% by echocardiography or
nuclear cardiography within three months of transplantation
- Adequate pulmonary function with corrected DLCO ≥ 40% by pulmonary function testing
within the past three months of transplantation
- Adequate renal function with creatinine clearance ≥ 30 ml/min. as calculated by the
Cockroft and Gault method.
- Adequate hepatic function with AST, ALT, alkaline phosphatase, and total bilirubin no
more than 3 x ULN unless related to neoplastic disease.
- Adequate vascular access, either by pheresis flow catheter or peripheral vein
intravenous catheter, to perform ECP, should the patient be randomized to ECP.
- Patients with prior autologous stem cell transplantation are eligible.
- Age 18 to 75 years.
- Life expectancy of greater than 3 months.
- ECOG performance status of 0, 1, or 2.
- Platelet counts ≥ 20,000/microliter, with or without transfusion support, at the time
of ECP, should the patient be randomized to ECP.
- Weight ≥ 40 kg.
- Systolic blood pressure ≥ 90 mmHg on the day randomization occurs
- Negative pregnancy test. The effects of ECP on the developing human fetus at the
recommended therapeutic dose are unknown. For this reason, women of childbearing
potential must agree to use adequate contraception (hormonal or barrier method of
birth control; abstinence) prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately.
- Able to receive 600 cGy of total body irradiation. If patient previously treated by
TBI then must be able to receive 400cGY of total body irradiation.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Hypersensitivity or allergy to 8-methoxypsoralen.
- Prior allogeneic stem cell transplantation
- HLA-DR mismatch or no worse than one antigen-mismatched unrelated donor.
- Patients with acute leukemia or acute lymphocytic leukemia with > 5% circulating
blasts in peripheral blood or > 5% blasts in bone marrow aspirate and biopsy at the
time of registration
- Patients with chemorefractory non-Hodgkin's lymphoma or Hodgkin's disease or multiple
myeloma
- Diagnosis of myelofibrosis
- Patients known to be positive for antibodies to HIC or have evidence for active HIC
viral replication.
- Participation in another clinical trial for prevention of GVHD.
- Patient is pregnant or lactating.
- Lack adequate vascular access for ECP.
- Systolic blood pressure < 90 mmHg at the time of randomization, should the patient be
randomized to ECP.
- Evidence of active, ongoing infection.
- Unwilling to comply with all study procedures.
- Unable or unwilling to give signed informed consent.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of grade 2-4 acute graft versus host disease following allogeneic stem cell transplantation in patients randomized to photopheresis vs. no photopheresis
Outcome Time Frame:
Day +100 following allogeneic stem cell transplant
Safety Issue:
No
Principal Investigator
Francine Foss, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Yale University
Authority:
United States: Institutional Review Board
Study ID:
0508000433
NCT ID:
NCT00402714
Start Date:
July 2006
Completion Date:
January 2010
Related Keywords:
- Hematologic Malignancies
- Allogeneic Stem Cell Transplant
- Neoplasms
- Hematologic Neoplasms
Name | Location |
|---|---|
| Yale Comprehensive Cancer Center at Yale University School of Medicine | New Haven, Connecticut 06520-8064 |
| Tufts-New England Medical Center | Boston, Massachusetts 02111 |
| Methodist Hospital - Texas Transplant Institute | San Antonio, Texas 78229 |
