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Sirolimus, Tacrolimus, and Antithymocyte Globulin in Preventing Graft-Versus-Host Disease in Patients With Hematologic Cancer Who Are Undergoing Donor Stem Cell Transplant

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00691015
First received: June 4, 2008
Last updated: May 26, 2017
Last verified: May 2017
  Purpose

RATIONALE: Giving low doses of chemotherapy, monoclonal antibodies, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop 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, and antithymocyte globulin before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of giving sirolimus together with tacrolimus and antithymocyte globulin and to see how well it works in preventing graft-versus-host disease in patients with hematologic cancer who are undergoing donor stem cell transplant.


Condition Intervention Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Biological: rituximab Drug: busulfan Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: fludarabine phosphate Drug: melphalan Radiation: total body irradiation (TBI) Drug: anti-thymocyte globulin IV Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Incidence of Acute Graft-versus-host Disease (GVHD) [ Time Frame: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria ]
  • Severity of Acute Graft-versus-host Disease (GVHD) [ Time Frame: Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria ]
  • Safety, as Defined by Serious Adverse Events and Adverse Events Related to Study Treatment. [ Time Frame: Within 6 months after PBSCT ]

Secondary Outcome Measures:
  • Incidence of Chronic GVHD. [ Time Frame: Within 2 years after PBSCT ]
  • Time to Engraftment (i.e., Absolute Neutrophil Recovery [ANC > 500/mm³] ) [ Time Frame: post transplant, up to 4 weeks ]
  • Overall Survival. [ Time Frame: At 2 years after PBSCT ]
  • Incidence of Infections, Including Bacterial, Fungal, and Viral Infections (i.e., CMV and EBV Reactivation, Including Post-transplant Lymphoproliferative Disorders) [ Time Frame: Within 6 months after PBSCT ]
  • Karnofsky Performance Status Performance Status [ Time Frame: At 90 days after PBSCT ]

    100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of their personal needs.

    50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent.

    20 - Very sick; hospital admission necessary; active supportive treatment necessary.

    10 - Moribund; fatal processes progressing rapidly. 0 - Dead



Enrollment: 48
Study Start Date: May 2008
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy or chemotherapy + total body irradiation

Standard of care (SOC) chemotherapy or ( SOC) chemotherapy + total body irradiation (TBI) of one of the following regimens:

Regimen I: Patients receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV.

Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8 fractions and receive etoposide IV;anti-thymocyte globulin IV.

Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive cyclophosphamide IV; anti-thymocyte globulin IV.

Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan IV; anti-thymocyte globulin IV.

Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and melphalan IV. Some patients also receive rituximab IV; anti-thymocyte globulin IV.

Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some patients also undergo TBI; anti-thymocyte globulin IV.

Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • MabThera
  • Zytux
Drug: busulfan
Given IV
Other Names:
  • Busulfex
  • Myleran
Drug: carmustine
Given IV
Other Names:
  • Bicnu
  • Gliadel
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Cytoxan Lyophilized
  • Neosar
Drug: cytarabine
Given IV
Other Name: Depocyt
Drug: etoposide
Given IV
Other Names:
  • Etopophos
  • Toposar
Drug: fludarabine phosphate
Given IV
Other Name: Fludara®
Drug: melphalan
Given IV
Other Name: Alkeran
Radiation: total body irradiation (TBI)
Given once or twice daily
Other Name: radiotherapy
Drug: anti-thymocyte globulin IV
Given IV
Other Name: Thymoglobulin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00691015

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
Study Chair: Zaid Al-Kadhimi, MD Barbara Ann Karmanos Cancer Institute
  More Information

Responsible Party: Zaid Al-Kadhimi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00691015     History of Changes
Other Study ID Numbers: 2007-127
P30CA022453 ( U.S. NIH Grant/Contract )
GENZ-WSU-2007-127
2007-127 ( Other Identifier: Barbara Ann Karmanos Cancer Institute )
Study First Received: June 4, 2008
Results First Received: December 9, 2015
Last Updated: May 26, 2017

Keywords provided by Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute:
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

Additional relevant MeSH terms:
Lymphoma
Syndrome
Leukemia
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Graft vs Host Disease
Myeloproliferative Disorders
Plasmacytoma
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Cyclophosphamide
Tacrolimus

ClinicalTrials.gov processed this record on August 17, 2017