Graft Versus Host DiseasePhase 2NCT00720629
Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
A Phase 2 study testing Visilizumab, Tacrolimus and Methotrexate in people with Graft Versus Host Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
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". Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Visilizumab, Tacrolimus and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- One of the following diagnoses with histological confirmation by the Pathology Department at H. Lee Moffitt Cancer Center:
- Acute Lymphocytic Leukemia (ALL) in complete remission 1 (CR1) with t(9:22) or t(4:11), or any ALL beyond CR1
- Acute Myelogenous Leukemia (AML) with high risk cytogenetics in CR1 as defined by Bloomfield any AML beyond CR1
- Myelodysplastic Syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1
- Chronic myelomonocytic leukemia (CMML)
- Chronic Myelogenous Leukemia (CML) with Imatinib-refractory chronic phase, or beyond chronic phase by morphology or cytogenetics
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- Myelofibrosis
- Severe aplastic anemia
- Chemosensitive Non-Hodgkin's lymphoma and Hodgkin's disease that are not candidate to autologous transplant due to prior autologous transplantation
- Multiple Myeloma patient not candidate for autologous stem cell transplantation
- Karnofsky performance status ≥ 70% (adult)
- Normal organ and marrow function as defined below:
- Hepatic: Total bilirubin must be less than or equal to 2mg/dL (Gilbert and other syndromes with increased indirect bilirubin are allowed); serum transaminases must be less than two times the upper limit of normal
- Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb), forced expiratory volume-one second (FEV1), forced vital capacity (FVC) must be greater than 50% predicted
- Cardiac: Left ventricular ejection fraction at rest must be greater than 50%
- Renal: Creatinine clearance (measured or calculated) must be equal or greater than 50 ml/min/1.73m^2
Who cannot join
- Anti thymocyte globulin (ATG) or anti T cell therapy in prior 45 days
- Splenectomized patients;
- A positive pregnancy test administered to all females of childbearing potential prior to allogeneic stem cell transplant
- Inability to comply with follow up as determined by the patient's physician
- HIV-I/II infection prior to hematopoietic stem cell (HSC) transplantation, confirmed by nucleic acid test (NAT)
- Uncontrolled bacterial or fungal infection
Show all 19Show fewer
- History of documented invasive aspergillosis or cytomegalovirus (CMV) pneumonia
- Presence of any of the following comorbid conditions:
- History of myocardial infarction
- Congestive heart failure (even if symptomatically controlled)
- Peripheral vascular disease (including intermittent claudication or history of bypass for arterial insufficiency)
- Untreated thoracic or abdominal aneurysm (6cm or more)
- History of any cerebrovascular accident including transient ischemic attacks
- Dementia
- History of peptic ulcer disease requiring treatment
- Connective tissue/rheumatologic disorders
- Diabetes unless being managed with dietary changes only
- Hemiplegia/paraplegia
- History of solid tumor excluding skin or cervical carcinoma after curative resection
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
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".
Read the detailed description
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".
- Conditions
- Graft Versus Host Disease
- Being tested
- Visilizumab, Tacrolimus, Methotrexate, Antithymocyte globulin (ATG)
- Keywords
- graft versus host disease, GVHD, allogeneic transplant, GVHD prevention, unrelated donors, mismatched unrelated donors, hematological malignancies, Leukemia, Lymphoma, Myelodysplastic Syndrome, Myelofibrosis, Aplastic Anemia, Multiple Myeloma
- Medical subject headings
- Graft vs Host Disease, Hematologic Neoplasms, Leukemia, Lymphoma, Myelodysplastic Syndromes, Primary Myelofibrosis, Anemia, Aplastic, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VisilizumabDrug
3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).
TacrolimusDrug
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.
MethotrexateDrug
15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Antithymocyte globulin (ATG)Drug
Also called Thymoglobulin-ATG
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.
TacrolimusDrug
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.
MethotrexateDrug
15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
| Study group | Role | What they receive |
|---|---|---|
| First Study Stage: Study Treatment | Experimental | Visilizumab, Tacrolimus and Methotrexate. Receives: Drug: Visilizumab; Drug: Tacrolimus; Drug: Methotrexate |
| Second Study Stage: Standard Treatment | Active comparator | 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. Receives: Drug: Antithymocyte globulin (ATG); Drug: Tacrolimus; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
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
Measured: 100 days
Secondary outcomes (5)
Incidence of Epstein-Barr Virus (EBV) Reactivation
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.
Measured: 3 months
Incidence of Rituximab Response to Reactivated EBV Without PTLD
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).
Measured: 100 days
Overall Survival (OS)
Median OS in days. Survival was measured from the time of transplant to the time of death.
Measured: At 2 years and 5 years
Pharmacodynamics of Visilizumab - Test 1
Mean Cmax (±SD)
Measured: At 1 - 2 hours
Pharmacodynamics of Visilizumab - Test 2
Mean terminal half-life (±SD)
Measured: Up to 205 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2008 (estimated)
- Study startDec 2007
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Lia Perez, MD, Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00720629
- Sponsor's protocol ID
- MCC-15033
- Other IDs
- R01CA132197-06A2
- Status last verified
- Apr 2014
- First submitted
- 21 Jul 2008
- Last updated
- 18 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pidala J, Perez L, Beato F, Anasetti C. Ustekinumab demonstrates activity in glucocorticoid-refractory acute GVHD. Bone Marrow Transplant. 2012 May;47(5):747-8. doi: 10.1038/bmt.2011.172. Epub 2011 Aug 29. No abstract available.
PubMed 21874061
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT00720629
- Acronym / sponsor ID
- MCC-15033
- Conditions
- Graft Versus Host Disease
- Keywords
- graft versus host disease, GVHD, allogeneic transplant, GVHD prevention, unrelated donors, mismatched unrelated donors, hematological malignancies, Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- Dec 2007
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 23 Jul 2008 (estimated)
- Results
- Posted 4 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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".
Detailed description
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".
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| First Study Stage: Study Treatment | Experimental | Drug: Visilizumab, Drug: Tacrolimus, Drug: MethotrexateVisilizumab, Tacrolimus and Methotrexate. |
| Second Study Stage: Standard Treatment | Active comparator | Drug: Antithymocyte globulin (ATG), Drug: Tacrolimus, Drug: MethotrexateSecond 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- One of the following diagnoses with histological confirmation by the Pathology Department at H. Lee Moffitt Cancer Center:
- Acute Lymphocytic Leukemia (ALL) in complete remission 1 (CR1) with t(9:22) or t(4:11), or any ALL beyond CR1
- Acute Myelogenous Leukemia (AML) with high risk cytogenetics in CR1 as defined by Bloomfield any AML beyond CR1
- Myelodysplastic Syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1
- Chronic myelomonocytic leukemia (CMML)
Key exclusion criteria (19 listed)
- Anti thymocyte globulin (ATG) or anti T cell therapy in prior 45 days
- Splenectomized patients;
- A positive pregnancy test administered to all females of childbearing potential prior to allogeneic stem cell transplant
- Inability to comply with follow up as determined by the patient's physician
- HIV-I/II infection prior to hematopoietic stem cell (HSC) transplantation, confirmed by nucleic acid test (NAT)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Visilizumab3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant). | Drug | First Study Stage: Study Treatment |
| Tacrolimus0.02 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. | Drug | First Study Stage: Study Treatment |
| Methotrexate15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant. | Drug | First Study Stage: Study Treatment |
| Antithymocyte globulin (ATG)Also: Thymoglobulin-ATG1 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. | Drug | Second Study Stage: Standard Treatment |
| Tacrolimus0.03 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. | Drug | Second Study Stage: Standard Treatment |
| Methotrexate15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant. | Drug | Second Study Stage: Standard Treatment |
Primary outcome
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days
Time frame: 100 days
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
5 secondary outcomes
Incidence of Epstein-Barr Virus (EBV) Reactivation
Time frame: 3 months
Incidence of Rituximab Response to Reactivated EBV Without PTLD
Time frame: 100 days
Overall Survival (OS)
Time frame: At 2 years and 5 years
Pharmacodynamics of Visilizumab - Test 1
Time frame: At 1 - 2 hours
Pharmacodynamics of Visilizumab - Test 2
Time frame: Up to 205 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21874061Pidala J, Perez L, Beato F, Anasetti C. Ustekinumab demonstrates activity in glucocorticoid-refractory acute GVHD. Bone Marrow Transplant. 2012 May;47(5):747-8. doi: 10.1038/bmt.2011.172. Epub 2011 Aug 29. No abstract available.
- H. Lee Moffitt Cancer Center \& Research InstituteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lia Perez, MD principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Visilizumab, Tacrolimus and Methotrexate in people with Graft Versus Host Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Grade II-IV Acute Graft-versus-Host Disease (GVHD) Score at 100 Days (time frame: 100 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00720629, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2014.