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Completed

NCT Number: NCT00185640

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

To measure how frequently and to what degree a complication of transplant cell acute graft versus host disease (GvHD) occurs.

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Key information

Conditions

Blood Cancer Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Leukemia Neoplasms Neoplasms by Histologic Type Neoplasms by Site

Age range

50 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Stanford University School of Medicine

Stanford, California, 94305, United States

About this study

This study evaluated whether 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

cyclosporine

Drug

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

Anti-thymocyte globulin (ATG)

Drug

1.5 mg/kg for total dose of 7.5mg/kg, IV starting on day -11 to day -7 before HCT

Other names: Thymoglobulin

Mycophenolate Mofetil (MMF)

Drug

Begins on day 0 after HCT at a dose of 15 mg/kg. Transplant recipients who received related donor grafts received MMF twice daily and those who received unrelated donor grafts received MMF 3 times daily.

Other names: CellCept

Filgrastim

Drug
  • Donors mobilized with 16 µg/kg/day filgrastim.
  • As needed, myelosuppression in transplant recipients will be managed with subcutaneous filgrastim 5 µg/kg/day

Other names: Neupogen, Granulocyte-colony stimulating factor (G-CSF; GCSF), colony-stimulating factor 3 (CSF-3)

Total lymphoid irradiation (TLI)

Radiation

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.

Primary outcomes

  1. 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 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 outcomes

  1. 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 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

  2. Incidence of Relapse

    Time frame: 3 years

    Reports the overall rate of disease relapse, occurring any time within 3 years after transplant

  3. Overall Survival (OS)

    Time frame: 3 and 5 years

  4. Event-free Survival (EFS)

    Time frame: 3 and 5 years

    Reports the number and proportion of participants who neither died due to any cause nor experienced relapse.

  5. 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.

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Registry information

Official study 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

Important dates

Study start
2003
Primary completion
2014
Study completion
2016
First posted
Sep 16, 2005
Registry last updated
Jun 29, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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