Clinical trial NCT00185640: Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Blood Cancer
Leukemia
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 303
Sex: ALL
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Acute Graft vs Host Disease (GvHD)
timeFrame: 100 days post-transplant
Secondary outcomes:
measure: Acute Graft vs Host Disease (GvHD), All Evaluable
timeFrame: 100 days post-transplant
measure: Incidence of Relapse
timeFrame: 3 years
measure: Overall Survival (OS)
timeFrame: 3 and 5 years
measure: Event-free Survival (EFS)
timeFrame: 3 and 5 years
measure: Transplant-related Mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Robert Lowsky
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.