Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant For Hematological Cancer - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00589563

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, antithymocyte globulin, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well sirolimus, tacrolimus, and antithymocyte globulin work in preventing graft-versus-host disease in patients undergoing a donor stem cell transplant for hematological cancer .

Condition	Intervention	Phase
Cancer-Related Problem/Condition Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition Small Intestine Cancer	Biological: anti-thymocyte globulin Drug: cyclophosphamide Drug: etoposide Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Drug: sirolimus Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: hematopoietic stem cell transplantation Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation	Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Hodgkin's Disease Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma Radiation Therapy

Drug Information available for: Cyclophosphamide Methotrexate Fludarabine Etoposide Sirolimus Fludarabine monophosphate Tacrolimus anhydrous Tacrolimus Melphalan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Supportive Care, Open Label
Official Title:	A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin, as Graft-Versus-Host Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Incidence and severity of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
Safety in the first 6 months post-transplant [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to absolute neutrophil count recovery (engraftment) [ Designated as safety issue: No ]
Time to platelet count recovery (engraftment) [ Designated as safety issue: No ]
Time to first hospital discharge [ Designated as safety issue: No ]
Incidence of infections including cytomegalovirus and Epstein-Barr virus reactivation [ Designated as safety issue: No ]
Incidence of thrombotic microangiopathy [ Designated as safety issue: No ]
Non-relapse mortality at 100 days and one year past hematopoietic stem cell transplantation (HSCT) [ Designated as safety issue: No ]
Overall and disease-free survival at one year post HSCT [ Designated as safety issue: No ]
Incidence of disease relapse [ Designated as safety issue: No ]
Incidence of post-transplant lymphoproliferative disease [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	May 2007
Estimated Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589563

Locations

United States, Arizona
Banner Good Samaritan Medical Center	Recruiting
Phoenix, Arizona, United States, 85006
Contact: Joseph Alvarnas, MD 602-239-4526 joseph.alvarnas@bannerhealth.com
United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Ryotaro Nakamura, MD

Beckman Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	City of Hope Comprehensive Cancer Center ( Ryotaro Nakamura )
Study ID Numbers:	CDR0000579340, CHNMC-06141
Study First Received:	December 21, 2007
Last Updated:	April 29, 2009
ClinicalTrials.gov Identifier:	NCT00589563 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Mantle Cell Lymphoma
Tacrolimus
Ileal Diseases
Graft Versus Host Disease
Preleukemia
Hemorrhagic Disorders
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Methotrexate
Etoposide
Myelodysplastic Myeloproliferative Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic

Blood Coagulation Disorders
Leukemia, Myeloid
Folic Acid
Leukemia, Myeloid, Accelerated Phase
Chronic Myelogenous Leukemia
Fludarabine
Lymphoma, Non-Hodgkin
Sirolimus
Immunologic Factors
Precancerous Conditions
Blood Protein Disorders
Lymphoma, Follicular
Lymphoblastic Lymphoma
Lymphoma, B-Cell
Anti-Bacterial Agents

Additional relevant MeSH terms:

Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Tacrolimus
Ileal Diseases
Duodenal Neoplasms
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Neoplasms by Site
Therapeutic Uses
Abortifacient Agents
Methotrexate
Cardiovascular Diseases

Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Immunoproliferative Disorders
Digestive System Neoplasms
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Abortifacient Agents, Nonsteroidal
Multiple Myeloma
Neoplasms
Gastrointestinal Neoplasms
Fludarabine
Lymphoma, Non-Hodgkin
Antimetabolites
Sirolimus

ClinicalTrials.gov processed this record on May 07, 2009