LeukemiaPhase 2NCT01323920
Bortezomib-based GVHD Prophylaxis After Allogeneic Transplant for Patients Without Matched Related Donors
A Phase 2 study testing Bortezomib, Tacrolimus and Methotrexate in people with Leukemia and Lymphoma, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Leukemia, Lymphoma, Myelodysplastic Syndrome
- What is being tested?
- Bortezomib, Tacrolimus and Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to Nov 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
- Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
- HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
- ECOG performance status 0-2
- Adequate organ function
- Able to understand and willing to sign a written informed consent document
- Agrees to practice adequate contraception per study requirements
Who cannot join
- Pregnant or breastfeeding
- Recipient of prior allogeneic or autologous stem cell transplantation
- Prior abdominal radiation therapy
- HIV-positive on combination antiretroviral therapy
- Seropositive for hepatitis B or C
- Allergies to bortezomib, boron, or mannitol
Show all 11Show fewer
- Myocardial infarction within last 6 months, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias
- Uncontrolled bacterial, viral or fungal infections
- Seizures or history of seizures
- History of another non-hematologic malignancy unless disease-free for at least 5 years
- Uncontrolled intercurrent illness
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study
A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.
In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.
Read the detailed description
Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.
You will receive 3 drugs for your GVHD prophylaxis:
Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.
Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.
Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.
- Conditions
- Leukemia, Lymphoma, Myelodysplastic Syndrome
- Being tested
- Bortezomib, Tacrolimus, Methotrexate
- Keywords
- Stem Cell Transplant, Allogeneic Transplant, Donors
- Medical subject headings
- Leukemia, Lymphoma, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Bortezomib 1.3 mg/m^2 IV
TacrolimusDrug
Tacrolimus 0.05 mg/kg PO bid
MethotrexateDrug
Methotrexate 15 mg/m^2 IV
| Study group | Role | What they receive |
|---|---|---|
| Velcade/Tac/MTX | Experimental | Drug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV
Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid
Drug: Methotrexate. Methotrexate 15 mg/m^2 IV Receives: Drug: Bortezomib; Drug: Tacrolimus; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.
Measured: Day 100
Secondary outcomes (3)
The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion
To assess the percentage donor engraftment up to day 30 post stem cell infusion, defined as the first of 3 consecutive days tested of documented absolute netrophil count (ANC) >/= 500 cells/u/L
Measured: Day 30
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion
Progression free and overall survival by 1 year after stem cell infusion will be assessed using the method of Kaplan and Meier. Progression-free survival will be defined as the time from stem cell infusion to the time of disease progression or death from any cause. Overall survival will be defined as the time from stem cell infusion to the time to death from any cause. Patients will be censored at the time last documented alive. Cumulative incidence and Kaplan-Meier curves will be constructed as appropriate. Progression is defined per clinical presentation, not protocol specified, and vary per disease, e.g. blasts in bone marrow or peripheral blood for AML/MDS; lymphoma + on PET/CT re-staging etc.
Measured: 1 year
The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2011 (estimated)
- Study startMay 2011
- Primary completionFeb 2013
- Study completionNov 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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Koreth, MD, Dana-Farber Cancer Institute
- Investigators
- John Koreth, MBBS, DPhil, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01323920
- Sponsor's protocol ID
- 11-007
- Status last verified
- May 2017
- First submitted
- 24 Mar 2011
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Koreth J, Kim HT, Lange PB, Bindra B, Reynolds CG, Chammas MJ, Armand P, Cutler CS, Ho VT, Glotzbecker B, Nikiforow S, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP 3rd. A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial. Biol Blood Marrow Transplant. 2015 Nov;21(11):1907-13. doi: 10.1016/j.bbmt.2015.05.027. Epub 2015 Jun 6.
PubMed 26055298
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bortezomib-based Graft-Versus-Host-Disease Prophylaxis After Myeloablative Allogeneic Stem Cell Transplantation for Patients Lacking HLA-matched Related Donors: A Phase 2 Study
- ClinicalTrials.gov ID
- NCT01323920
- Acronym / sponsor ID
- 11-007
- Conditions
- Leukemia, Lymphoma, Myelodysplastic Syndrome
- Keywords
- Stem Cell Transplant, Allogeneic Transplant, Donors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- May 2011
- Primary completion
- Feb 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 28 Mar 2011 (estimated)
- Results
- Posted 31 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A common problem after stem cell transplant is graft-versus-host-disease (GVHD). GVHD is a complication of transplantation where the donor graft attacks and damages some of your tissues. After stem cell transplant, all patients receive prophylactic medications against GVHD.
In this research study, we are studying the safety and effectiveness of a bortezomib based GVHD prophylaxic drug combination in participants after myeloablative allogeneic stem call transplantation from a matched unrelated donor, mismatched related or unrelated donor.
Detailed description
Before your transplant you will receive conditioning therapy with fludarabine and busulfan given 7, 6, 5, and 4 days before your transplant. On day 0, you will receive selected blood cells taken from your sibling or unrelated donor.
You will receive 3 drugs for your GVHD prophylaxis:
Tacrolimus will be started 3 days before your transplant. It will be given intravenously and later by mouth. You will continue to take tacrolimus for 3 to 6 months after transplant.
Methotrexate will be given intravenously 1, 3, 6 and 11 days after your transplant.
Bortezomib will be given intravenously 1, 4, and 7 days after your transplant. On days 1, 4, 7, 30 and 3, 6 and 12 months after your transplant you will have a physical exam, blood work, and be asked to complete a questionnaire.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Velcade/Tac/MTX | Experimental | Drug: Bortezomib, Drug: Tacrolimus, Drug: MethotrexateDrug: Bortezomib. Other Names: Velcade. Bortezomib 1.3 mg/m^2 IV Drug: Tacrolimus. Tacrolimus 0.05 mg/kg PO bid Drug: Methotrexate. Methotrexate 15 mg/m^2 IV |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Histologically or cytologically confirmed advanced and/or aggressive hematologic malignancy (including myelodysplastic syndrome) that is unlikely to be cured by alternative therapies
- HLA-Matched unrelated donor; or 1-locus HLA-mismatched related or unrelated donor
- ECOG performance status 0-2
- Adequate organ function
- Able to understand and willing to sign a written informed consent document
Key exclusion criteria (11 listed)
- Pregnant or breastfeeding
- Recipient of prior allogeneic or autologous stem cell transplantation
- Prior abdominal radiation therapy
- HIV-positive on combination antiretroviral therapy
- Seropositive for hepatitis B or C
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 |
|---|---|---|
| BortezomibAlso: VelcadeBortezomib 1.3 mg/m^2 IV | Drug | Velcade/Tac/MTX |
| TacrolimusTacrolimus 0.05 mg/kg PO bid | Drug | Velcade/Tac/MTX |
| MethotrexateMethotrexate 15 mg/m^2 IV | Drug | Velcade/Tac/MTX |
Primary outcome
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion
Time frame: Day 100
The primary outcome of this study is the cumulative incidence of grade II-IV acute GVHD up to Day 100 after stem cell infusion. Acute GHVD is graded according to the modified Glucksberg criteria (adapted from Thomas et al., NEJM ,1975, pp. 895-90), which is based on criteria by which the provider classifies acute GVHD per its objective organ staging. Acute GVHD is assessed in weekly standard of care visits post stem cell infusion and is captured in the protocol EDC upon evaluation of clinical notes up to Day 100. Data for acute GVHD organ staging and etiologies are collected in an acute GVHD separate case report form and do not include system organ class, expectedness or attribution.
3 secondary outcomes
The Percentage Donor Engraftment up to Day 30 Post Stem Cell Infusion
Time frame: Day 30
The Non-relapse Mortality, Progression-free and Overall Survival up to 1 Year After Stem Cell Infusion
Time frame: 1 year
The Cumulative Incidence of Chronic GVHD Requiring Systemic Immune Suppression up to 1 Year After Stem Cell Infusion
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26055298Koreth J, Kim HT, Lange PB, Bindra B, Reynolds CG, Chammas MJ, Armand P, Cutler CS, Ho VT, Glotzbecker B, Nikiforow S, Ritz J, Blazar BR, Soiffer RJ, Antin JH, Alyea EP 3rd. A Bortezomib-Based Regimen Offers Promising Survival and Graft-versus-Host Disease Prophylaxis in Myeloablative HLA-Mismatched and Unrelated Donor Transplantation: A Phase II Trial. Biol Blood Marrow Transplant. 2015 Nov;21(11):1907-13. doi: 10.1016/j.bbmt.2015.05.027. Epub 2015 Jun 6.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
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.
John Koreth, MBBS, DPhil principal investigator
Dana-Farber Cancer 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 Bortezomib, Tacrolimus and Methotrexate in people with Leukemia and Lymphoma, run by Dana-Farber Cancer 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 6 inclusion and 11 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 30 May 2017. 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 31 Mar 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?
The Cumulative Incidence of Grade II-IV Acute GVHD up to Day 100 After Stem Cell Infusion (time frame: Day 100). 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 NCT01323920, 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 30 May 2017.