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Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00185640
First Posted: September 16, 2005
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Robert Lowsky, Stanford University
  Purpose
To measure how frequently and to what degree a complication of transplant cell acute graft versus host disease (GvHD) occurs.

Condition Intervention Phase
Blood Cancer Leukemia Drug: Cyclosporine Drug: Anti-Thymocyte Globulin Drug: mycophenolate mofetil Drug: Granulocyte-Colony Stimulating Factor Radiation: Total Lymphoid Irradiation Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Cell Transplantation Using a Non-Myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-Thymocyte Globulin for Older Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Robert Lowsky, Stanford University:

Primary Outcome Measures:
  • Acute Graft vs Host Disease (GvHD) [ Time Frame: 100 days post-transplant ]

    The incidence of acute GvHD after transplantation was assessed per Glucksberg GvHD grade, a compound scale based on the following combinations of disease stages.

    Skin manifestations Skin Stages

    • 0: No rash
    • 1: Maculopapular (MP) rash <25% of body surface area
    • 2: MP rash on 25-50% of body surface area
    • 3: Generalized erythroderma (ED)
    • 4: Generalized ED with bullous formation and desquamation

    Liver Stages (Bilirubin in mg/dL)

    • 0: <2
    • 1: 2-3
    • 2: 3.01-6
    • 3: 6.01-15.0
    • 4: >15

    Gastrointestinal (GI) Stages (diarrhea)

    • 0: None or < 500 mL/day
    • 1: 500-999 mL/day
    • 2: 1000-1499 mL/day
    • 3: >1500 mL/day
    • 4: Severe abdominal pain, with or without ileus

    Glucksberg Overall grade

    • Grade 1: Skin 1/2; GI 0; Liver 0; Karnofsky performance scale (KPS) 90-100%.
    • Grade 2: Skin 1-3; GI 1; Liver 1; KPS 70-80
    • Grade 2: Skin 2/3; GI 2/3; Liver 2-4; KPS 50-60
    • Grade 4: Skin 2-4; GI 2-4; Liver 2-4; KPS 30-40


Secondary Outcome Measures:
  • Acute Graft vs Host Disease (GvHD), All Evaluable [ Time Frame: 100 days post-transplant ]

    The incidence of acute GvHD after transplantation was assessed per Glucksberg GvHD grade, a compound scale based on the following combinations of disease stages.

    Skin manifestations Skin Stages

    • 0: No rash
    • 1: Maculopapular (MP) rash <25% of body surface area
    • 2: MP rash on 25-50% of body surface area
    • 3: Generalized erythroderma (ED)
    • 4: Generalized ED with bullous formation and desquamation

    Liver Stages (Bilirubin in mg/dL)

    • 0: <2
    • 1: 2-3
    • 2: 3.01-6
    • 3: 6.01-15.0
    • 4: >15

    Gastrointestinal (GI) Stages (diarrhea)

    • 0: None or < 500 mL/day
    • 1: 500-999 mL/day
    • 2: 1000-1499 mL/day
    • 3: >1500 mL/day
    • 4: Severe abdominal pain, with or without ileus

    Glucksberg Overall grade

    • Grade 1: Skin 1/2; GI 0; Liver 0; Karnofsky performance scale (KPS) 90-100%.
    • Grade 2: Skin 1-3; GI 1; Liver 1; KPS 70-80
    • Grade 2: Skin 2/3; GI 2/3; Liver 2-4; KPS 50-60
    • Grade 4: Skin 2-4; GI 2-4; Liver 2-4; KPS 30-40

  • Incidence of Relapse [ Time Frame: 3 years ]
    Reports the overall rate of disease relapse, occurring any time within 3 years after transplant

  • Overall Survival (OS) [ Time Frame: 3 and 5 years ]
  • Event-free Survival (EFS) [ Time Frame: 3 and 5 years ]
    Reports the proportion of subjects who neither died due to any cause nor experienced relapse.

  • Transplant-related Mortality [ Time Frame: 1 year ]
    Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.


Enrollment: 303
Study Start Date: March 2003
Study Completion Date: January 2016
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Non-myeloablative transplantation
Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) infusion of the donor graft Post-transplant immunosuppression with cyclosporine and mycophenolate mofetil .
Drug: Cyclosporine
starting day -3 at a dose of 5 mg/kg orally twice daily with a target trough level of 350 to 450 ng/mL
Other Names:
  • Cyclosporin
  • Cyclosporin A
Drug: Anti-Thymocyte Globulin
1.5 mg/kg for total dose of 7.5mg/kg, IV starting on day -11 to day -7 before HCT
Other Names:
  • Thymoglobulin
  • ATG
Drug: mycophenolate mofetil
Begins on day 0 after HCT at a dose of 15 mg/kg. Patients who received related donor grafts received MMF twice daily and those who received unrelated donor grafts received MMF 3 times daily.
Other Names:
  • CellCept
  • MMF
Drug: Granulocyte-Colony Stimulating Factor
Received on day 0
Other Names:
  • Filgrastim
  • colony-stimulating factor 3
  • csf 3
  • G-CSF
  • GCSF
Radiation: Total Lymphoid Irradiation
0.8 Gy/day from day -11 to day -7 (inclusive) from day -4 to day -2 (inclusive) with 2 additional fractions of 0.8 Gy delivered on day -1 for total dose of 8 Gy.
Other Name: TLI

Detailed Description:
This study will evaluate if TLI-ATG conditioning followed by allogeneic hematpoietic cell transplant (HCT), which has provided excellent overall survival for patients with relapsed lymphoma after failed autologous HCT, provides a similar benefit in the setting of elderly patients with hematologic malignancies.
  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Any patient with one of the following hematolymphoid malignancies or syndromes in whom allogeneic hematopoietic stem cell transplant (HST) is warranted. Specific disease categories include:

    • Indolent advanced stage non-Hodgkin lymphomas
    • Mantle cell lymphoma
    • Chronic lymphocytic leukemia
    • Hodgkin disease (Hodgkin's lymphoma)
    • Acute leukemias in complete remission
    • Aplastic anemia
    • Paroxysmal nocturnal hemoglobinuria
    • Myelodysplastic or myeloproliferative syndromes.
    • Other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
  • Age > 50 years, or if < 50 years of age, considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants due to pre-existing medical conditions or prior therapy.
  • A fully human leukocyte antigen (HLA)-identical sibling or matched unrelated donor is available. Potential participants with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
  • Participant must be competent to give consent.

EXCLUSION CRITERIA:

  • Progressive hematolymphoid malignancies despite conventional therapies, or acute leukemias not in complete remission.
  • Uncontrolled central nervous system (CNS) involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Pregnant
  • Cardiac ejection fraction < 30%
  • Uncontrolled cardiac failure
  • Pulmonary diffusing capacity (DLCO) < 40% predicted
  • Elevation of bilirubin to > 3 mg/dL
  • Transaminases > 4 x the upper limit of normal
  • Creatinine clearance < 50 cc/min (24-hour urine collection)
  • Karnofsky performance score < 60%
  • Poorly controlled hypertension on multiple antihypertensives
  • Documented fungal disease that is progressive despite treatment
  • HIV-positive. Other viral infections, ie, Hepatitis B- and C- positive, evaluated on a case-by-case basis
  • Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00185640


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Robert Lowsky Stanford University
  More Information

Publications:

Responsible Party: Robert Lowsky, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00185640     History of Changes
Obsolete Identifiers: NCT00186615
Other Study ID Numbers: IRB-11960
78998 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT153 ( Other Identifier: OnCore )
First Submitted: September 12, 2005
First Posted: September 16, 2005
Results First Submitted: December 1, 2016
Results First Posted: October 3, 2017
Last Update Posted: October 3, 2017
Last Verified: February 2015
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
Cyclosporins
Cyclosporine
Mycophenolic Acid
Thymoglobulin
Antilymphocyte Serum
Lenograstim
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Adjuvants, Immunologic