A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin, as Graft-versus-Host Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
Phase 2
2 Years
N/A
2 Years
N/A
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Infection, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Precancerous Condition, Secondary Myelofibrosis, Small Intestine Cancer
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Infection, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Precancerous Condition, Secondary Myelofibrosis, Small Intestine Cancer
Trial Information
A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin, as Graft-versus-Host Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
OBJECTIVES:
Primary
- To determine the incidence and severity of acute- and chronic-graft-versus-host disease
(GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood
transplantation in patients with hematologic malignancies scheduled to receive
immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as
GVHD prophylaxis.
- To determine the safety of this combination in the first six months post-transplant.
Secondary
- To determine the time-to-engraftment, non-relapse mortality rate, overall and
disease-free survival, incidence of disease relapse, and incidence of opportunistic
infections with this GVHD prophylaxis.
OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate
and melphalan vs fractionated total-body irradiation [FTBI] and etoposide vs FTBI and
cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).
- Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning
on day -9 or -8 and continuing to day -1 or 0.
- Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched
unrelated donor peripheral blood stem cells on day 0.
- Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously
beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2,
anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate* IV on days
1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper).
NOTE: *Only patients with high-risk HLA mismatch receive treatment with methotrexate.
After completion of study therapy, patients are followed periodically for up to 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of hematological malignancy including any of the following:
- Non-Hodgkin lymphoma (NHL) in any complete remission (CR) or partial response
(PR)
- Hodgkin lymphoma in any CR or PR
- Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in any CR
- Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood
absolute blast count < 500/µL on the day of initiation of conditioning for
patients with non-CR AML or ALL
- Myelodysplastic syndromes (MDS) treated or untreated
- Chronic myelogenous leukemia (CML) in chronic or accelerated phase
- Multiple myeloma in any CR or PR
- Chronic lymphocytic leukemia in CR or PR 2 or greater
- Myelofibrosis and other myeloproliferative disorders
- Bone marrow blasts < 20% within 4 weeks of transplant and peripheral blood
absolute blast count < 500/µL on the day of initiation
- High-risk disease defined as AML or ALL > CR1, accelerated phase CML, recurrent
aggressive lymphoma, or active lymphoproliferative disease at transplant
- Low-risk disease defined as AML or ALL in CR1, chronic phase CML, or low-grade
lymphoproliferative disorder with controlled disease at transplant
- Must be planning to receive 1 of the following conditioning regimens at City of Hope:
- Fludarabine phosphate and melphalan for patients with hematological malignancies
and contraindications for conventional myeloablative regimens due to age,
co-morbidity, or previous transplant
- Fractionated total-body irradiation (FTBI) and etoposide for patients with AML
and ALL or CML in accelerated phase
- FTBI and cyclophosphamide for patients with NHL, AML, CML, and MDS
- Suitable unrelated donor available
- HLA-matched or mismatched
- Peripheral blood stem cells available
- No bone marrow or ex vivo-engineered or processed graft (e.g., CD34-positive,
T-cell depletion)
- No uncontrolled CNS disease
PATIENT CHARACTERISTICS:
- Karnofsky performance status (PS) 70-100% or ECOG PS 0-2
- Creatinine < 1.3 mg/dL or creatinine clearance ≥ 70 mL/min
- Ejection fraction > 45%
- Direct bilirubin < 3 times upper limit of normal (ULN)
- ALT and AST < 3 times ULN
- Forced vital capacity, FEV1, and DLCO > 45% of predicted
- Able to cooperate with oral medication intake
- No active donor or recipient serology positive for HIV
- No known contraindication to administration of sirolimus, tacrolimus, or
anti-thymocyte globulin
- No active hepatitis B or C
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Concurrent participation in other clinical trials for prevention or treatment of
viral, bacterial, or fungal disease allowed provided agents do not interact with
agents used in the current study
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Outcome Measure:
Incidence and severity of acute and chronic graft-versus-host disease
Outcome Time Frame:
6 months after transplant
Safety Issue:
No
Principal Investigator
Ryotaro Nakamura, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
06141
NCT ID:
NCT00589563
Start Date:
May 2007
Completion Date:
February 2012
Related Keywords:
- Chronic Myeloproliferative Disorders
- Graft Versus Host Disease
- Infection
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- Precancerous Condition
- Secondary Myelofibrosis
- Small Intestine Cancer
- graft versus host disease
- infection
- adult favorable prognosis Hodgkin lymphoma
- adult unfavorable prognosis Hodgkin lymphoma
- childhood favorable prognosis Hodgkin lymphoma
- childhood unfavorable prognosis Hodgkin lymphoma
- cutaneous B-cell non-Hodgkin lymphoma
- recurrent adult Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- stage I adult Hodgkin lymphoma
- stage I childhood Hodgkin lymphoma
- stage I cutaneous T-cell non-Hodgkin lymphoma
- stage II adult Hodgkin lymphoma
- stage II childhood Hodgkin lymphoma
- stage II cutaneous T-cell non-Hodgkin lymphoma
- stage III adult Hodgkin lymphoma
- stage III childhood Hodgkin lymphoma
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV childhood Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- anaplastic large cell lymphoma
- angioimmunoblastic T-cell lymphoma
- Burkitt lymphoma
- contiguous stage II adult Burkitt lymphoma
- contiguous stage II adult diffuse large cell lymphoma
- contiguous stage II adult diffuse mixed cell lymphoma
- contiguous stage II adult diffuse small cleaved cell lymphoma
- contiguous stage II adult immunoblastic large cell lymphoma
- contiguous stage II adult lymphoblastic lymphoma
- contiguous stage II grade 1 follicular lymphoma
- contiguous stage II grade 2 follicular lymphoma
- contiguous stage II grade 3 follicular lymphoma
- contiguous stage II mantle cell lymphoma
- contiguous stage II marginal zone lymphoma
- contiguous stage II small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell 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
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult T-cell leukemia/lymphoma
- recurrent childhood anaplastic large cell lymphoma
- recurrent childhood grade III lymphomatoid granulomatosis
- recurrent childhood lymphoblastic lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent grade I lymphomatoid granulomatosis
- recurrent grade II lymphomatoid granulomatosis
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- small intestine lymphoma
- splenic marginal zone lymphoma
- stage I adult Burkitt lymphoma
- stage I adult diffuse large cell lymphoma
- stage I adult diffuse mixed cell lymphoma
- stage I adult diffuse small cleaved cell lymphoma
- stage I adult immunoblastic large cell lymphoma
- stage I adult lymphoblastic lymphoma
- stage I adult T-cell leukemia/lymphoma
- 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 immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage III childhood anaplastic large cell lymphoma
- stage III childhood lymphoblastic lymphoma
- stage III childhood small noncleaved cell 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 immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult T-cell leukemia/lymphoma
- stage IV childhood anaplastic large cell lymphoma
- stage IV childhood lymphoblastic lymphoma
- stage IV childhood small noncleaved cell 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
- 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)
- childhood acute myeloid leukemia in remission
- recurrent adult acute myeloid leukemia
- recurrent childhood acute myeloid leukemia
- secondary acute myeloid leukemia
- adult acute lymphoblastic leukemia in remission
- childhood acute lymphoblastic leukemia in remission
- recurrent adult acute lymphoblastic leukemia
- recurrent childhood acute lymphoblastic leukemia
- accelerated phase chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- refractory chronic lymphocytic leukemia
- relapsing chronic myelogenous leukemia
- stage I chronic lymphocytic leukemia
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- childhood myelodysplastic syndromes
- de novo myelodysplastic syndromes
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- atypical chronic myeloid leukemia, BCR-ABL negative
- chronic myelomonocytic leukemia
- juvenile myelomonocytic leukemia
- primary myelofibrosis
- secondary myelofibrosis
- Primary Myelofibrosis
- Neoplasms
- Graft vs Host Disease
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Precancerous Conditions
- Lymphoma, Large-Cell, Immunoblastic
- Duodenal Neoplasms
- Ileal Neoplasms
- Jejunal Neoplasms
- Lymphoma, Large-Cell, Anaplastic
- Intestinal Neoplasms
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
| Banner Good Samaritan Medical Center | Phoenix, Arizona 85006 |
