Tacrolimus and ATG as GVHD Prophylaxis in Patients Undergoing Related Donor HSCT
Status: | Completed |
---|---|
Conditions: | Cancer, Cancer, Cancer, Cancer, Blood Cancer, Infectious Disease, Lymphoma, Women's Studies, Hematology |
Therapuetic Areas: | Hematology, Immunology / Infectious Diseases, Oncology, Reproductive |
Healthy: | No |
Age Range: | 18 - 70 |
Updated: | 3/30/2013 |
Start Date: | November 2010 |
End Date: | April 2015 |
A Phase II Study of Tacrolimus and Thymoglobulin, as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Related Donor Hematopoietic Cell Transplantation
This phase II trial studies how well giving tacrolimus and anti-thymocyte globulin together
works in preventing graft-vs-host disease (GVHD) in patients with hematologic malignancies
undergoing donor peripheral blood stem cell transplant (PBSCT). Sometimes the transplanted
cells from a donor can make an immune response against the body's normal cells. Giving
tacrolimus together with anti-thymocyte globulin may stop this from happening
PRIMARY OBJECTIVES:
I. To determine the incidence and severity of acute GVHD (aGVHD) following human leukocyte
antigen (HLA) matched related donor hematopoietic peripheral blood transplant in patients
with hematologic malignancies that receive the immunosuppressive combination of Tacrolimus
and Thymoglobulin (anti-thymocyte globulin) as GVHD prophylaxis.
II. To determine the safety of this combination in the first six months post transplant.
SECONDARY OBJECTIVES:
I. To determine engraftment time of neutrophils (absolute neutrophil count > 0.5 x 10^9/L
for 3 consecutive days), and platelets (platelet count > 20 X 10^9/L for 3 consecutive
days).
II. To determine incidence of opportunistic infections, defined as infection that occurs in
people with weakened immune systems and caused by an organism that does not normally cause
disease. These include: fungal infections, pneumocytics carinii pneumonia (PCP), and viral
infections (cytomegalovirus [CMV], varicella zoster virus [VZV], herpes simplex virus [HSV],
BK virus [BK], Epstein-Barr virus [EBV], including post-transplant lymphoproliferative
disorder [PTLD]).
III. To estimate incidence of chronic GVHD (cGVHD) at two years. IV. To determine overall
and disease free survival at two years. V. To assess immune response with immunocorrelative
studies both pre and at various points post transplant.
OUTLINE:
GVHD PROPHYLAXIS: Patients receive tacrolimus intravenously (IV) continuously or orally (PO)
on days -3 to 60 with taper to day 100 (high-risk disease) or on days -3 to 100 with taper
to day 180 (low-risk disease). Patients also receive anti-thymocyte globulin IV over 4-6
hours on days -3 to -1.
PREPARATIVE REGIMEN: Patients receive standard of care (at the Karmanos Cancer Institute)
preparative regimens chosen by the treating physician, based on diagnosis.
TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.
After completion of study treatment, patients are followed up for 2 years.
Inclusion Criteria:
- Suitable related donor as determined by the treating physician
- High resolution molecular HLA typing is mandatory for HLA Class I and II
- Diagnosis of hematological malignancy
- Patients with one of the following hematologic malignancies, and felt to be
transplant candidates by their treating physician are eligible to enroll on this
protocol:
- Non-Hodgkin lymphoma, any complete remission (CR)/partial remission (PR)
- Hodgkin disease, any CR/PR/stable disease (SD)
- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) any CR; for non-CR
AML or ALL, bone marrow blast < 20% within 4 weeks of transplant and peripheral blood
(PB) absolute blast count < 500/μl on the day of initiation of conditioning
- Myelodysplastic syndrome (MDS), treated or untreated
- Chronic myelogenous leukemia (CML) in chronic phase or accelerated phase
- Chronic myelomonocytic leukemia (CMML)
- Multiple myeloma, any CR/PR/SD
- Chronic lymphocytic leukemia (CLL) any CR/PR
- Myelofibrosis and other myeloproliferative disorders; bone marrow blasts less than 20
percent within four weeks of transplant and peripheral blood absolute blast counts
less than 500 per microliter on the day of initiation of conditioning
- Age >= 18 and able to cooperate with oral medication intake
- Filgrastim (G-CSF) mobilized Peripheral blood stem cells
- Agrees to participate, and informed consent signed
- Karnofsky performance status (KPS) >= 60, Eastern Cooperative Oncology Group (ECOG)
performance status =< 2
- Creatinine clearance > 60 mL/min
- Ejection fraction > 50%
- Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)
less than 3 X upper limit of normal
- Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) or
diffusion capacity of carbon monoxide (DLCO) > 50% predicted
Exclusion Criteria:
- Bone marrow or Ex vivo engineered or processed graft (cluster of differentiation
[CD]34+ enrichment, T-cell depletion, etc)
- Patients with documented uncontrolled central nervous system (CNS) disease
- Active donor or recipient serology positive for human immunodeficiency virus (HIV)
- Known contraindication to administration of Tacrolimus or Thymoglobulin
- Active Hepatitis B or C
- Patients with coronary heart disease (recent myocardial infarctions, angina, cardiac
stent, or bypass surgery in the last 6 months) need to be cleared with a stress
echocardiogram or nuclear myocardial perfusion stress test, and cardiology consult;
all other cardiac history will be at the discretion of the Principal Investigator
- Oxygen usage at the time of enrollment
- Patients with clinical ascites
- Women who are pregnant or nursing
We found this trial at
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Barbara Ann Karmanos Cancer Institute Karmanos is based in southeast Michigan, in midtown Detroit, and...
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