Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Lymphoma

Leukemia

Hematologic Neoplasms

Anemia

Anemia, Aplastic

Graft vs Host Disease

Preleukemia

Myelodysplastic Syndromes

Primary Myelofibrosis

Lymphosarcoma

Aplastic Anemia

Homologous Wasting Disease

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Methotrexate

Tacrolimus

Thymoglobulin

Antilymphocyte Serum

Visilizumab

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Folinic Acid

Folate

Vitamin B9

Visilizumab, Tacrolimus and Methotrexate.

Second Stage: Antithymocyte-globulin (ATG), Tacrolimus and Methotrexate. The study was closed during first stage and did not proceed to the second stage comparison to ATG in combination with tacrolimus/methotrexate as originally planned.

3 mg/m\^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).

0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.

15 mg/m\^2 intravenously (IV) on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant.

Antithymocyte globulin (ATG)

0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.

15 mg/m\^2 IV on Day 1 after transplant; 10 mg/m\^2 IV on Days 3, 6 and 11 after transplant.

Lia Perez, MD

The purpose of this study was to test whether a new drug named visilizumab would decrease the severity of graft-versus-host disease in patients treated with a mismatched donor. Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as the "study treatment".

The protocol plan was a two stage, controlled, phase II study to assess safety and compare the grade of acute graft-versus-host disease (GVHD) with visilizumab, or Anti-thymocyte Globulin (ATG) in combination with tacrolimus + methotrexate in patients at high risk of GVHD after transplant from unrelated donors mismatched for 1-2 alleles of any type at human leukocyte antigen (HLA) A, B, C and DRB1.

The study design included two stages. The first stage of the trial was to enroll 15 patients on a single arm to be treated with "study treatment" (visilizumab, tacrolimus and methotrexate) to assess for treatment safety and exclude intolerable GVHD. The second stage of the trial was to include a random control group of patients treated with the current "standard treatment" (ATG, tacrolimus, and methotrexate) or "study treatment". The purpose of this comparison was to determine if the "study treatment" visilizumab causes less severe side effects and if it is more potent in reducing graft-versus-host disease symptoms than the "standard treatment".

Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation

Cumulative Incidence of Grade II-IV Acute GVHD Score at 100 Days. Investigators had planned to assess whether the grade of acute GVHD was decreased by visilizumab in combination with tacrolimus/methotrexate compared to standard treatment with thymoglobulin/tacrolimus/methotrexate after transplantation from unrelated mismatched donors, from day of transplant up to one year. Study was closed during the first treatment stage and did not proceed to the second stage treatment comparison to ATG in combination with tacrolimus/methotrexate as originally planned.

Overall GVHD Grade: From Filipovich AH, Weisdorf D, Pavletic S, etal: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 11:945-955 (2005). Grade I: Skin Stage 1-2, Liver Stage 0, Gut State 0; Grade II: Skin Stage 3 or, Liver Stage 1 or, Gut Stage 1; Grade II

Number of participants who reactivated EBV. Patients had their plasma tested once weekly using the TaqMan polymerase chain reaction (PCR) for quantitative determination of EBV-DNA for 6 weeks. Plasma levels \> 1000 copies per ml plasma were scored as positive.

Participants who developed plasma EBV-DNA of \>1000 copies/mL on any tests received rituximab.

Incidence of Rituximab Response: Reactivated EBV participants whose plasma titers cleared after rituximab, without post-transplant lymphoproliferative disorder (PTLD).

Median OS in days. Survival was measured from the time of transplant to the time of death.

National Institutes of Health (NIH)

National Cancer Institute (NCI)

H. Lee Moffitt Cancer Center and Research Institute

The time of administration of visilizumab on Day 1 through Day 360. Per protocol, expected transplant/GVHD-related (other than serious) adverse event details were not tabulated in the same manner as serious adverse events.

Visilizumab, Tacrolimus and Methotrexate. All participants.

First Stage: Study Treatment

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

First Stage: Study Treatment. All participants.

Study closed early during the first stage, did not proceed to the second stage comparison as planned. Investigators exercised right to close the study prematurely for lack of efficacy, although no protocol-defined end points had been met.

Lia Perez, M.D.

Grade II-IV Acute GVHD

Grade I-II Acute GVHD

Grade III-IV Acute GVHD

First Study Stage: Study Treatment

Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days

Incidence of Epstein-Barr Virus (EBV) Reactivation

Incidence of Rituximab Response to Reactivated EBV Without PTLD

First Study Stage: Study Treatment. Visilizumab, Tacrolimus and Methotrexate.

2 Year Analysis Group

5 Year Analysis Group

Participants who had died by Year 2 and additional participants who had died by Year 5.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation	NCT00720629	Graft Versus Ho...	Visilizumab Tacrolimus Methotrexate Antithymocyte g... Tacrolimus Methotrexate	18 Years - 60 Years	H. Lee Moffitt Cancer Center and Research Institute
Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation	NCT00720629	Graft Versus Ho...	Visilizumab Tacrolimus Methotrexate Antithymocyte g... Tacrolimus Methotrexate	18 Years - 60 Years	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for mismatched unrelated donors