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CompletedNCT00185640Updated Jun 29, 2021Results posted

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

A Phase 2 interventional study of Cyclosporine and Anti-thymocyte globulin (ATG) in Blood Cancer and Leukemia, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 50 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-06-29.

Sponsored by Stanford University · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
303
Allocation
Not applicable
Ages
50 Years to 70 Years
Sex
All
01

Study summary

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

Read the detailed description

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.

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Conditions studied

  • Blood Cancer
  • Leukemia
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In context

Hematologic Neoplasms

1,464 studies on the registry are indexed under Hematologic Neoplasms; 433 are open to participants now.

This study's enrollment of 303 is above the median of 45 across 1,068 interventional studies indexed under Hematologic Neoplasms.

Browse Hematologic Neoplasms studies →

Lead sponsor

Stanford University is the lead sponsor of 2,117 studies on the registry; 425 are open to participants now.

Of its 259 completed or terminated interventional studies of FDA-regulated products, 197 (76%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
303 participants (actual)

Study arms

  • Experimental
    Non-myeloablative transplantation

    Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil.

    Drug: Cyclosporine · Drug: Anti-thymocyte globulin (ATG) · Drug: Mycophenolate mofetil (MMF) · Drug: Filgrastim · Radiation: Total Lymphoid Irradiation (TLI)

Interventions

  • DrugCyclosporine

    Starting day -3 at a dose of 5 mg/kg orally twice daily with a target trough level of 350 to 450 ng/mL

    Also known as: Cyclosporin, Cyclosporin A

  • DrugAnti-thymocyte globulin (ATG)

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

    Also known as: Thymoglobulin

  • DrugMycophenolate mofetil (MMF)

    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.

    Also known as: CellCept

  • DrugFilgrastim

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

    Also known as: Neupogen, Granulocyte-colony stimulating factor (G-CSF; GCSF), colony-stimulating factor 3 (CSF-3)

  • RadiationTotal Lymphoid Irradiation (TLI)

    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.

06

What researchers measure

Primary outcomes

  1. Acute Graft vs Host Disease (GvHD)

    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

    Time frame: 100 days post-transplant

Secondary outcomes

  1. Acute Graft vs Host Disease (GvHD), All Evaluable

    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

    Time frame: 100 days post-transplant

  2. Incidence of Relapse

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

    Time frame: 3 years

  3. Overall Survival (OS)

    Time frame: 3 and 5 years

  4. Event-free Survival (EFS)

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

    Time frame: 3 and 5 years

  5. Transplant-related Mortality

    Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.

    Time frame: 1 year

07

Results

Posted Oct 3, 2017

Participant flow

Participant flow — Overall Study
MilestoneNon-myeloablative Transplantation
Started303
Transplanted296
90 days post-transplant161
Completed158
Not completed145
Withdrew: Not eligible4
Withdrew: Withdrawal by subject3
Withdrew: Death138

Outcome measures

PrimaryAcute Graft vs Host Disease (GvHD)

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

Time frame:
100 days post-transplant
Reported as:
Number · percentage of participants
Acute Graft vs Host Disease (GvHD)
percentage of participantsNon-myeloablative Transplantation
Acute Graft vs Host Disease (GvHD)2.7
SecondaryAcute Graft vs Host Disease (GvHD), All Evaluable

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

Time frame:
100 days post-transplant
Reported as:
Number · percentage of participants
Acute Graft vs Host Disease (GvHD), All Evaluable
percentage of participantsNon-myeloablative Transplantation
Acute Graft vs Host Disease (GvHD), All Evaluable11
SecondaryIncidence of Relapse

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

Time frame:
3 years
Reported as:
Number · percentage of participants
Incidence of Relapse
percentage of participantsNon-myeloablative Transplantation
Incidence of Relapse53
SecondaryOverall Survival (OS)
Time frame:
3 and 5 years
Reported as:
Number · percentage of participants
Overall Survival (OS)
percentage of participantsNon-myeloablative Transplantation
3 years70
5 years64
SecondaryEvent-free Survival (EFS)

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

Time frame:
3 and 5 years
Reported as:
Count of participants · Participants
Event-free Survival (EFS)
ParticipantsNon-myeloablative Transplantation
3 years44
5 years38
SecondaryTransplant-related Mortality

Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.

Time frame:
1 year
Reported as:
Number · percentage of participants
Transplant-related Mortality
percentage of participantsNon-myeloablative Transplantation
Transplant-related Mortality6

Adverse events

Collected over 5 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Non-myeloablative Transplantation138/303 (45.5%)138/303 (45.5%)55/303 (18.2%)
Most frequent serious events
Most frequent serious events
EventNon-myeloablative Transplantation
DeathsGastrointestinal disorders138/303
Most frequent other events
Most frequent other events
EventNon-myeloablative Transplantation
Secondary malignancySkin and subcutaneous tissue disorders26/303
Secondary malignancyBlood and lymphatic system disorders22/303
Secondary malignancyGastrointestinal disorders4/303
Secondary malignancyReproductive system and breast disorders2/303
Secondary malignancyRespiratory, thoracic and mediastinal disorders1/303

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Non-myeloablative Transplantation
<=18 years0
Between 18 and 65 years260
>=65 years43
Sex: Female, Male
Sex: Female, Male(Participants)Non-myeloablative Transplantation
Female128
Male175
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Non-myeloablative Transplantation
Hispanic or Latino20
Not Hispanic or Latino276
Unknown or Not Reported7
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Non-myeloablative Transplantation
American Indian or Alaska Native0
Asian37
Native Hawaiian or Other Pacific Islander7
Black or African American6
White233
More than one race0
Unknown or Not Reported20
Histology
Histology(participants)Non-myeloablative Transplantation
Acute Biphenotypic Leukemia1
Acute Leukemia, Nos1
Acute Monocytic Leukemia2
Acute Myeloid Leukemia84
Acute Promyelocytic Leukemia4
Angioimmunoblastic T-Cell Lymphoma1
B lymphoblastic leukemia/lymphoma, NOS1
B-Cell Chr. Lymph. Leuk./Small Lymph. Lymphoma45
Chronic Myelogenous Leukemia, Bcr/Abl Positive1
Chronic Myeloid Leukemia, Nos8
Chronic Myeloproliferative Disease, Nos2
Cutaneous T-Cell Lymphoma, Nos1
Follicular Lymphoma, Grade 1-34
Hodgkin Lymphoma, Nodular Sclerosis, Nos4
Hodgkin Lymphoma, Nos20
Malignant Lymphoma, Non-Hodgkin86
Mantle Cell Lymphoma10
Marginal Zone B-Cell Lymphoma, Nos2
Mature T-Cell Lymphoma, Nos1
Ml, Large B-Cell, Diffuse2
Ml, Small B Lymphocytic, Nos1
Myelodysplastic Syndrome, Nos3
Precursor Cell Lymphoblastic Leukemia, Nos15
Prolymphocytic Leukemia, Nos1
Prolymphocytic Leukemia, T-Cell Type1
Subcutaneous Panniculitis-Like T-Cell Lymphoma1
Unknown1
08

Study locations

1 site
  • Stanford University School of Medicine
    Stanford, California 94305, United States
09

References and documents

Publications

  • Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, Laport GG, Stockerl-Goldstein KE, Johnston LJ, Hoppe RT, Bloch DA, Blume KG, Negrin RS, Strober S. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005 Sep 29;353(13):1321-31. doi: 10.1056/NEJMoa050642. Erratum In: N Engl J Med. 2006 Feb 23;354(8):884. PubMed 16192477 ↗
  • Jones CD, Arai S, Lowsky R, Tyan DB, Zehnder JL, Miklos DB. Complete donor T-cell engraftment 30 days after allogeneic transplantation predicts molecular remission in high-risk chronic lymphocytic leukaemia. Br J Haematol. 2010 Sep;150(5):637-9. doi: 10.1111/j.1365-2141.2010.08252.x. Epub 2010 Jun 7. No abstract available. PubMed 20528878 ↗
  • Rezvani AR, Kanate AS, Efron B, Chhabra S, Kohrt HE, Shizuru JA, Laport GG, Miklos DB, Benjamin JE, Johnston LJ, Arai S, Weng WK, Negrin RS, Strober S, Lowsky R. Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning. Bone Marrow Transplant. 2015 Oct;50(10):1286-92. doi: 10.1038/bmt.2015.149. Epub 2015 Jul 6. PubMed 26146806 ↗
  • Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009 Jul 30;114(5):1099-109. doi: 10.1182/blood-2009-03-211441. Epub 2009 May 7. PubMed 19423725 ↗
  • Benjamin J, Chhabra S, Kohrt HE, Lavori P, Laport GG, Arai S, Johnston L, Miklos DB, Shizuru JA, Weng WK, Negrin RS, Lowsky R. Total lymphoid irradiation-antithymocyte globulin conditioning and allogeneic transplantation for patients with myelodysplastic syndromes and myeloproliferative neoplasms. Biol Blood Marrow Transplant. 2014 Jun;20(6):837-43. doi: 10.1016/j.bbmt.2014.02.023. Epub 2014 Mar 7. PubMed 24607552 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 29, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00185640
Lead sponsor
Stanford University
Responsible party
Robert Lowsky (Professor of Medicine, Stanford University) — Principal investigator
First posted
Sep 16, 2005
Start date
Mar 2003
Primary completion
Apr 2014
Completion
Jan 2016
Results posted
Oct 3, 2017
Last update
Jun 29, 2021

Study contacts

Robert Lowsky
principal investigator · Stanford University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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