A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
18 Years
N/A
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
OBJECTIVES:
Primary
- To determine the incidence and severity of acute graft-versus-host disease (GVHD) after
HLA-matched or -mismatched unrelated donor peripheral blood stem cell transplantation
(PBSCT) in patients with hematologic malignancies treated with immunosuppressive
therapy comprising sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD
prophylaxis.
- To determine the safety of this regimen in these patients at 6 months after PBSCT.
Secondary
- To determine the time to engraftment (i.e., platelet and absolute neutrophil recovery)
in patients treated with this regimen.
- To determine the length of hospital stay of these patients within 100 days after PBSCT.
- To determine the incidence of infections, including CMV and EBV reactivation and
post-transplant lymphoproliferative disorders, in patients treated with this regimen.
- To determine the incidence of thrombotic microangiopathy and veno-occlusive disease in
patients treated with this regimen.
- To determine the incidence of chronic GVHD in patients treated with this regimen.
- To determine the overall and disease-free survival of these patients at 2 years after
PBSCT.
- To determine the Karnofsky performance status of these patients at baseline and at
various time points after PBSCT.
- To conduct immunocorrelative studies prior to and at various time points after PBSCT.
OUTLINE:
- Conditioning regimen: Patients receive 1 of 6 conditioning regimens between days -9 and
-3, based on diagnosis and the treating physician's preference regarding regimen
intensity.
- Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
- Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8
fractions and receive etoposide IV.
- Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive
cyclophosphamide IV.
- Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan
IV.
- Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and
melphalan IV. Some patients also receive rituximab IV.
- Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some
patients also undergo TBI.
- Allogeneic peripheral blood stem cell transplantation: Patients undergo filgrastim
(G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.
- Graft-versus-host disease prophylaxis (GVHD): Patients receive tacrolimus IV
continuously over 24 hours or orally and sirolimus orally beginning on day -3 and
continuing until day 30 or day 90, followed by a taper in the absence of GVHD. Patients
also receive anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
Blood samples are obtained at baseline and periodically during study for correlative
biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number
quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution,
T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after
transplantation, and regulatory T-cell reconstitution.
After completion of study therapy, patients are followed periodically for up to 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of a hematological malignancy, including any of the following:
- Non-Hodgkin lymphoma in complete remission (CR) or partial remission (PR)
- Hodgkin lymphoma in CR or PR
- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) meeting
either of the following criteria:
- In CR
- Not in CR and meets the following criteria:
- Bone marrow blast < 20% within 4 weeks of transplantation
- Peripheral blood absolute blast count < 500 per microliter on the day
of initiating conditioning therapy
- Myelodysplastic syndromes, treated or untreated
- Chronic myeloid leukemia in chronic phase or accelerated phase
- Multiple myeloma in CR or PR
- Chronic lymphocytic leukemia in second or greater CR or PR
- Myelofibrosis or other myeloproliferative disorders meeting the following
criteria:
- Bone marrow blasts < 20% within 4 weeks of transplantation
- Peripheral blood absolute blast count < 500 per microliter on the day of
initiating conditioning therapy
- Patients with ascites not allowed
- No prior bone marrow or ex vivo engineered or processed graft (i.e., CD34+
enrichment, T-cell depletion, etc)
- Scheduled to undergo peripheral blood stem cell transplantation from a suitable
HLA-matched or -mismatched unrelated donor, as determined by treating physician
- High resolution molecular HLA typing is required for HLA class I and II
- No more than one antigen or allele mismatch
- No documented uncontrolled CNS disease
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2
- Karnofsky PS 60-100%
- Creatinine clearance > 50 mL/min
- Bilirubin < 3 times upper limit of normal (ULN)
- ALT and AST < 3 times ULN
- LVEF > 50%
- FVC, FEV_1, or DLCO > 50% predicted
- Patients on home oxygen not allowed
- Able to cooperate with oral medication intake
- HIV negative
- No active hepatitis B or hepatitis C
- No known contraindication to sirolimus, tacrolimus, or anti-thymocyte globulin
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Incidence and severity of acute graft-versus-host disease (GVHD)
Outcome Time Frame:
Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
Safety Issue:
No
Principal Investigator
Zaid Al-Kadhimi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Barbara Ann Karmanos Cancer Institute
Authority:
United States: Federal Government
Study ID:
CDR0000597130
NCT ID:
NCT00691015
Start Date:
May 2008
Completion Date:
January 2014
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- stage III adult Burkitt lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult Hodgkin lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage III small lymphocytic lymphoma
- stage IV adult Burkitt lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- accelerated phase chronic myelogenous leukemia
- adult acute lymphoblastic leukemia in remission
- adult acute myeloid leukemia in remission
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- chronic phase chronic myelogenous leukemia
- recurrent adult acute lymphoblastic leukemia
- recurrent adult acute myeloid leukemia
- secondary acute myeloid leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- de novo myelodysplastic syndromes
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- primary myelofibrosis
- atypical chronic myeloid leukemia, BCR-ABL negative
- chronic eosinophilic leukemia
- chronic myelomonocytic leukemia
- chronic neutrophilic leukemia
- Neoplasms
- Graft vs Host Disease
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
