Non-Hodgkin's LymphomaPhase 2NCT00709592
Reduced Intensity Total Body Irradiation + Thymoglobulin Followed by Allogeneic PBSCT
A Phase 2 study testing Thymoglobulin, Total-Body Irradiation and Allogeneic PBSCT or BMT in people with Non-Hodgkin's Lymphoma and Leukemia, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
One of two different doses of thymoglobulin will allow bone marrow engraftment with minimal Graft-versus-Host Disease and allow adequate immune response to allow the transplanted stem cells to replace the tumor cells. Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Leukemia, Multiple Myeloma
- What is being tested?
- Thymoglobulin, Total-Body Irradiation and Allogeneic PBSCT or BMT
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2008to 28 Jun 2017
- 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 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with hematological malignancies for which allogeneic stem cell transplantation indicated including non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute myeloid leukemia (AML), Hodgkin lymphoma (HD), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS)
- Patients with HLA compatible related or unrelated stem cell donor, willing and able to serve as an allogenic HSC donor. Unrelated donors have to be matched at HLA-A, B, C and DRB1 loci. A single locus mismatch will be tolerated in the event a more closely matched donor is not available.
- Patients age >/=40 to </=70 with an ECOG performance status < 2
- Patients between 18 and 40 years of age will be eligible only if they have co-morbidities precluding conventional allogeneic transplantation with full intensity myeloablative conditioning
- Adequate cardiac, pulmonary, renal and hepatic function for transplant
- Negative serology for HIV
Show all 9Show fewer
- Negative serum pregnancy test
- Patients who have received therapeutic radiation to a localized field will be eligible, provided critical structure tolerance doses have not been exceeded
- Patients who have had prior myeloablative autologous transplant will be eligible
Who cannot join
- Evidence of uncontrolled viral, fungal, bacterial infection
- Evidence of active meningeal or CNS disease
- Prior therapy with rabbit ATG, prior treatment with equine ATG is allowed if more than 3 months ago
- Breast feeding mothers are excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298-0037
About this study
Official title: Reduced Intensity Myeloablative Total Body Irradiation and Thymoglobulin Followed by Allogeneic Peripheral Blood Stem Cell Transplantation
One of two different doses of thymoglobulin will allow bone marrow engraftment with minimal Graft-versus-Host Disease and allow adequate immune response to allow the transplanted stem cells to replace the tumor cells.
Read the detailed description
This randomized phase II trial studies how well giving low dose total-body irradiation (TBI) with anti-thymocyte globulin followed by donor peripheral blood stem cell transplant (PBSCT) works in treating patients with hematologic malignancies. Giving reduced intensity total-body irradiation and anti-thymocyte globulin before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with antithymocyte globulin before transplant may stop this from happening.
- Conditions
- Non-Hodgkin's Lymphoma, Leukemia, Multiple Myeloma, Acute Myeloid Leukemia, Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Being tested
- Thymoglobulin, Total-Body Irradiation, Allogeneic PBSCT or BMT, Tacrolimus, Mycophenolate Mofetil
- Keywords
- total body irradiation, Allogeneic Peripheral Blood Stem Cell Transplantation, thymoglobulin
- Medical subject headings
- Lymphoma, Non-Hodgkin, Leukemia, Multiple Myeloma, Leukemia, Myeloid, Acute, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinBiological
Also called anti-thymocyte globulin (rabbit), ATG, Genzyme, anti-thymocyte globulin
Patients eligible for participation in this study will be randomized between receiving rabbit ATG for 3 days. Thymoglobulin will be administered according to VCU BMT standard of care starting day -9 and continued daily through day -7.
Total-Body IrradiationRadiation
Also called Whole-Body Irradiation, Total Body Irradiation [TBI]
Undergo TBI
Allogeneic PBSCT or BMTProcedure or surgery
Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Blood Stem Cell Transplantation [Allogenic PBSCT], Allogeneic Bone Marrow Transplantation [BMT]
Undergo allogeneic PBSCT or BMT
TacrolimusDrug
Also called Fujimycin, Hecoria, Prograf, Protopic
Given PO
Also called CellCept, MMF
Given PO
| Study group | Role | What they receive |
|---|---|---|
| ATG 1.7 mg/kg, TBI, transplant | Experimental | (Rabbit-ATG;Thymoglobulin,Genzyme) ATG 5.1 mg/kg in three divided doses (1.7 mg/kg/d) given over three days (day -9 to -7) followed by 450 cGy TBI and tacrolimus plus MMF GVHD prophylaxis. Patients receive lower dose anti-thymocyte globulin IV on days -9 to -7. Patients undergo total-body radiation (TBI) twice daily (BID) on day -1 and once daily (QD) on day 0. Patients then undergo peripheral blood stem cells or bone marrow transplant on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: patients receive tacrolimus orally (PO) on days -2 to 90-120 with taper for 2 months, and mycophenolate mofetil (MMF) PO BID on days 0-30. Receives: Biological: Thymoglobulin; Radiation: Total-Body Irradiation; Procedure: Allogeneic PBSCT or BMT; Drug: Tacrolimus; Drug: Mycophenolate Mofetil |
| ATG 2.5 mg/kg/d, TBI, transplant | Experimental | (Rabbit-ATG;Thymoglobulin,Genzyme) ATG 7.5 mg/kg in three divided doses (2.5 mg/kg/d) given over three days (day -9 to -7) followed by 450 cGy TBI and tacrolimus plus MMF GVHD prophylaxis. Patients receive higher dose anti-thymocyte globulin intravenously (IV) on days -9 to -7. Patients undergo total-body radiation (TBI) twice daily (BID) on day -1 and once daily (QD) on day 0. Patients then undergo peripheral blood stem cells or bone marrow transplant on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: patients receive tacrolimus orally (PO) on days -2 to 90-120 with taper for 2 months, and mycophenolate mofetil (MMF) PO BID on days 0-30. Receives: Biological: Thymoglobulin; Radiation: Total-Body Irradiation; Procedure: Allogeneic PBSCT or BMT; Drug: Tacrolimus; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Comparison of Functional Immune Reconstitution at 6-9 Months Following Transplant as Measured by Antibody Response to Vaccination With Inactivated Hepatitis A or B Vaccine.
A positive test result will indicate immune reconstitution, while a negative test results will indicate lack of immune reconstitution. Participants not done (ND) will be counted with the negative (Neg).
Measured: Up to 9 months following transplant
Secondary outcomes (8)
Engraftment of Donor Hematopoietic Stem Cells, as Measured by Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT.
Measured: Up to 52 weeks post transplant.
Survival
Measured: 2-year survival rate (%)
Treatment Related Mortality
Measured: Day 100
Event-free Survival
Measured: 2 years
Relapse
Patients with different disease relapses was determined according to current clinical standards based on the disease. For example, AML or MDS relapse is determined by a bone marrow biopsy. Multiple myeloma relapse requires a number of labs and/or biopsy to diagnose such as SPEP, UPEP, immunofixation, serum and urine light chains. In lymphoma disease is followed using CT and/or PET scans.
Measured: 2 year relapse rate (%)
Donor Lymphocyte Infusion
Measured: 2 year rate of DLI
Acute Graft-Versus-Host Disease (GVHD)
Measured: 2 year rate (%)
Chronic Graft-Versus-Host Disease (GVHD)
Measured: 2 year GVHD rate
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2008 (estimated)
- Study start21 Jul 2008
- Primary completion15 Feb 2014
- Study completion28 Jun 2017
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.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Amir Toor, MD, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00709592
- Sponsor's protocol ID
- MCC-11561
- Other IDs
- NCI-2011-01698
- Status last verified
- Nov 2018
- First submitted
- 1 Jul 2008
- Last updated
- 9 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Myeloablative Total Body Irradiation and Thymoglobulin Followed by Allogeneic Peripheral Blood Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT00709592
- Acronym / sponsor ID
- MCC-11561
- Conditions
- Non-Hodgkin's Lymphoma, Leukemia, Multiple Myeloma, Acute Myeloid Leukemia, Hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Keywords
- total body irradiation, Allogeneic Peripheral Blood Stem Cell Transplantation, thymoglobulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- 21 Jul 2008 (actual)
- Primary completion
- 15 Feb 2014 (actual)
- Study completion
- 28 Jun 2017 (actual)
- First posted
- 3 Jul 2008 (estimated)
- Results
- Posted 12 Feb 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One of two different doses of thymoglobulin will allow bone marrow engraftment with minimal Graft-versus-Host Disease and allow adequate immune response to allow the transplanted stem cells to replace the tumor cells.
Detailed description
This randomized phase II trial studies how well giving low dose total-body irradiation (TBI) with anti-thymocyte globulin followed by donor peripheral blood stem cell transplant (PBSCT) works in treating patients with hematologic malignancies. Giving reduced intensity total-body irradiation and anti-thymocyte globulin before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with antithymocyte globulin before transplant may stop this from happening.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATG 1.7 mg/kg, TBI, transplant | Experimental | Biological: Thymoglobulin, Radiation: Total-Body Irradiation, Procedure: Allogeneic PBSCT or BMT, Drug: Tacrolimus, Drug: Mycophenolate Mofetil(Rabbit-ATG;Thymoglobulin,Genzyme) ATG 5.1 mg/kg in three divided doses (1.7 mg/kg/d) given over three days (day -9 to -7) followed by 450 cGy TBI and tacrolimus plus MMF GVHD prophylaxis. Patients receive lower dose anti-thymocyte globulin IV on days -9 to -7. Patients undergo total-body radiation (TBI) twice daily (BID) on day -1 and once daily (QD) on day 0. Patients then undergo peripheral blood stem cells or bone marrow transplant on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: patients receive tacrolimus orally (PO) on days -2 to 90-120 with taper for 2 months, and mycophenolate mofetil (MMF) PO BID on days 0-30. |
| ATG 2.5 mg/kg/d, TBI, transplant | Experimental | Biological: Thymoglobulin, Radiation: Total-Body Irradiation, Procedure: Allogeneic PBSCT or BMT, Drug: Tacrolimus, Drug: Mycophenolate Mofetil(Rabbit-ATG;Thymoglobulin,Genzyme) ATG 7.5 mg/kg in three divided doses (2.5 mg/kg/d) given over three days (day -9 to -7) followed by 450 cGy TBI and tacrolimus plus MMF GVHD prophylaxis. Patients receive higher dose anti-thymocyte globulin intravenously (IV) on days -9 to -7. Patients undergo total-body radiation (TBI) twice daily (BID) on day -1 and once daily (QD) on day 0. Patients then undergo peripheral blood stem cells or bone marrow transplant on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: patients receive tacrolimus orally (PO) on days -2 to 90-120 with taper for 2 months, and mycophenolate mofetil (MMF) PO BID on days 0-30. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with hematological malignancies for which allogeneic stem cell transplantation indicated including non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute myeloid leukemia (AML), Hodgkin lymphoma (HD), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS)
- Patients with HLA compatible related or unrelated stem cell donor, willing and able to serve as an allogenic HSC donor. Unrelated donors have to be matched at HLA-A, B, C and DRB1 loci. A single locus mismatch will be tolerated in the event a more closely matched donor is not available.
- Patients age >/=40 to </=70 with an ECOG performance status < 2
- Patients between 18 and 40 years of age will be eligible only if they have co-morbidities precluding conventional allogeneic transplantation with full intensity myeloablative conditioning
- Adequate cardiac, pulmonary, renal and hepatic function for transplant
Key exclusion criteria (4 listed)
- Evidence of uncontrolled viral, fungal, bacterial infection
- Evidence of active meningeal or CNS disease
- Prior therapy with rabbit ATG, prior treatment with equine ATG is allowed if more than 3 months ago
- Breast feeding mothers are excluded
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 |
|---|---|---|
| ThymoglobulinAlso: anti-thymocyte globulin (rabbit), ATG, Genzyme, anti-thymocyte globulinPatients eligible for participation in this study will be randomized between receiving rabbit ATG for 3 days. Thymoglobulin will be administered according to VCU BMT standard of care starting day -9 and continued daily through day -7. | Biological | ATG 1.7 mg/kg, TBI, transplant, ATG 2.5 mg/kg/d, TBI, transplant |
| Total-Body IrradiationAlso: Whole-Body Irradiation, Total Body Irradiation [TBI]Undergo TBI | Radiation | ATG 1.7 mg/kg, TBI, transplant, ATG 2.5 mg/kg/d, TBI, transplant |
| Allogeneic PBSCT or BMTAlso: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Blood Stem Cell Transplantation [Allogenic PBSCT], Allogeneic Bone Marrow Transplantation [BMT]Undergo allogeneic PBSCT or BMT | Procedure or surgery | ATG 1.7 mg/kg, TBI, transplant, ATG 2.5 mg/kg/d, TBI, transplant |
| TacrolimusAlso: Fujimycin, Hecoria, Prograf, ProtopicGiven PO | Drug | ATG 1.7 mg/kg, TBI, transplant, ATG 2.5 mg/kg/d, TBI, transplant |
| Mycophenolate MofetilAlso: CellCept, MMFGiven PO | Drug | ATG 1.7 mg/kg, TBI, transplant, ATG 2.5 mg/kg/d, TBI, transplant |
Primary outcome
The Comparison of Functional Immune Reconstitution at 6-9 Months Following Transplant as Measured by Antibody Response to Vaccination With Inactivated Hepatitis A or B Vaccine.
Time frame: Up to 9 months following transplant
A positive test result will indicate immune reconstitution, while a negative test results will indicate lack of immune reconstitution. Participants not done (ND) will be counted with the negative (Neg).
8 secondary outcomes
Engraftment of Donor Hematopoietic Stem Cells, as Measured by Time in Days to Neutrophil and Platelet Count Recovery Following Allogeneic PBSCT.
Time frame: Up to 52 weeks post transplant.
Survival
Time frame: 2-year survival rate (%)
Treatment Related Mortality
Time frame: Day 100
Event-free Survival
Time frame: 2 years
Relapse
Time frame: 2 year relapse rate (%)
Donor Lymphocyte Infusion
Time frame: 2 year rate of DLI
Acute Graft-Versus-Host Disease (GVHD)
Time frame: 2 year rate (%)
Chronic Graft-Versus-Host Disease (GVHD)
Time frame: 2 year GVHD rate
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- VCU Massey Cancer CenterLink 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.
Amir Toor, MD principal investigator
Massey Cancer Center
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 Thymoglobulin, Total-Body Irradiation and Allogeneic PBSCT or BMT in people with Non-Hodgkin's Lymphoma and Leukemia, run by Virginia Commonwealth University 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 9 inclusion and 4 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: finished, as of the sponsor's last update on 9 Nov 2018. 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 12 Feb 2015). 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?
The Comparison of Functional Immune Reconstitution at 6-9 Months Following Transplant as Measured by Antibody Response to Vaccination With Inactivated Hepatitis A or B Vaccine. (time frame: Up to 9 months following transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Nov 2018.