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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00185640
• Other study ID #: IRB-11960
• Secondary ID: 78998BMT153
• Status: Completed
• Phase: Phase 2
• Start date: March 2003
• Est. completion date: January 2016

Study information

• Verified date: June 2021
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Other known NCT identifiers

• NCT00186615

Recruitment information / eligibility

• Status: Completed
• Enrollment: 303
• Est. completion date: January 2016
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Blood Cancer
• Hematologic Neoplasms
• Leukemia

Intervention

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
• Anti-thymocyte globulin (ATG)
1.5 mg/kg for total dose of 7.5mg/kg, IV starting on day -11 to day -7 before HCT
• Mycophenolate 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.
• Filgrastim
Donors mobilized with 16 µg/kg/day filgrastim. As needed, myelosuppression in transplant recipients will be managed with subcutaneous filgrastim 5 µg/kg/day

Radiation:
• Total 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.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 — View 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: 10.1 — View 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 reaction — View 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 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	100 days post-transplant
Secondary	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	100 days post-transplant
Secondary	Incidence of Relapse	Reports the overall rate of disease relapse, occurring any time within 3 years after transplant	3 years
Secondary	Overall Survival (OS)		3 and 5 years
Secondary	Event-free Survival (EFS)	Reports the number and proportion of participants who neither died due to any cause nor experienced relapse.	3 and 5 years
Secondary	Transplant-related Mortality	Reports the proportion of participants who expired within 1 year due to any complication or failure of the transplant.	1 year