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

Stanford University

Status and phase: Completed; Phase 2

Conditions: Blood Cancer; Leukemia

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

Study type: Interventional

Funder types: Other

Identifiers

NCT00185640

IRB-11960

78998 (Other Identifier)

BMT153 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 303 patients

Sex: All

Ages: 50 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

303 participants in 1 patient group

Non-myeloablative transplantation

Experimental group

Description:

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.

Treatment:

Drug: Cyclosporine

Drug: Mycophenolate mofetil (MMF)

Radiation: Total Lymphoid Irradiation (TLI)

Drug: Anti-thymocyte globulin (ATG)

Drug: Filgrastim