Acute LeukemiaPhase 2NCT02877082
Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients
A Phase 2 study testing Thymoglobulin, Bortezomib and Tacrolimus in people with Acute Leukemia and Chronic Lymphocytic Leukemia, run by Emory University at 1 site in United States.
Trial summary
This phase II trial studies how well tacrolimus, bortezomib, and anti-thymocyte globulin (thymoglobulin) work in preventing low toxicity graft versus host disease (GVHD) in patients with blood cancer who are undergoing donor stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Leukemia, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- What is being tested?
- Thymoglobulin, Bortezomib and Tacrolimus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to Jul 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disorder and myelodysplasia with no circulating blasts and with less than 5% blasts in the bone marrow within 4 weeks of the start of transplant conditioning regimen
- Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma; follicular, marginal zone, diffuse large B-cell or mantle cell lymphoma with chemo-sensitive disease at time of transplant
- Patients must have a related or unrelated peripheral blood stem cell donor; sibling donor must be a 6/6 match for human leukocyte antigen (HLA)-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation; unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing; unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to National Marrow Donor Program (NMDP) criteria
- Cardiac function: ejection fraction > 40%
- Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
- Pulmonary function: carbon monoxide diffusing capability test (DLCO) ≥ 40% (adjusted for hemoglobin) and forced expiratory volume in 1 second (FEV1) ≥ 50%
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- Total bilirubin < 1.5 x the upper limit of normal; patients who have been diagnosed with Gilbert's disease are allowed to exceed the defined bilirubin value of 1.5 x the upper limit of normal
- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper normal limit
- Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception or agree to completely abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
- Male subjects (even if surgically sterilized), of partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
- Signed informed consent
Who cannot join
- Prior allogeneic transplant
- Karnofsky performance score < 70%
- Active central nervous system (CNS) involvement by malignant cells
- Patients with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
- Patients with transformed lymphoma (e.g., Richter's transformation arising in follicular lymphoma or chronic lymphocytic leukemia)
- Patients seropositive for the human immunodeficiency virus (HIV)
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- Patient with active hepatitis B or C
- Patients with hypersensitivity to bortezomib, boron, or mannitol
- Patients with > grade 2 sensory peripheral neuropathy
- Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiography (ECG) abnormality at screening must be documented by the investigator as not medically relevant
- Female patients who are lactating or pregnant
- Patients with a serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent > 5 years previously will be allowed; cancer treated with curative intent < 5 years previously will not be allowed unless approved by the protocol officer or one of the protocol chairs
Trial locations and contacts
1 site in 1 country.
United States1 site
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Phase II Trial of Low Toxicity GVHD Prevention and Enhanced Immune Recovery With Tacrolimus, Bortezomib and Thymoglobulin® TBT
This phase II trial studies how well tacrolimus, bortezomib, and anti-thymocyte globulin (thymoglobulin) work in preventing low toxicity graft versus host disease (GVHD) in patients with blood cancer who are undergoing donor stem cell transplant. Tacrolimus and anti-thymocyte globulin may reduce the risk of the recipient's body rejecting the transplant by suppressing the recipient's immune system. Giving bortezomib after the transplant may help prevent GVHD by stopping the donor's cells from attacking the recipient. Giving tacrolimus, bortezomib, and anti-thymocyte globulin may be a better way to prevent low toxicity GVHD in patients with blood cancer undergoing donor stem cell transplant.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine a composite end point of alive and severe acute GVHD free at 6 months following human leukocyte antigen (HLA) matched related or unrelated donor hematopoietic peripheral blood transplant in patients with hematologic malignancies who receive the immunosuppressive combination tacrolimus, bortezomib, anti-thymocyte globulin (TBT) as GVHD prophylaxis.
II. To determine the safety of this combination in the first six months post-transplant.
SECONDARY OBJECTIVES:
- To determine the cumulative incidence of grade III-IV aGVHD.
II. To determine incidence and severity of chronic GVHD.
III. To determine disease relapse or progression overall and disease free survival at one year.
OUTLINE:
Patients receive tacrolimus intravenously (IV) on day -3 through day 180. Patients may receive tacrolimus orally (PO) later at the doctor's discretion. Patients receive anti-thymocyte globulin IV on days -3, -2, and -1 and bortezomib IV on day 0 and day 3. Patients undergo allogeneic bone marrow transplant on day 0.
After completion of study treatment, patients are followed up for 6 months and then periodically for up to 2 years.
- Conditions
- Acute Leukemia, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Graft Versus Host Disease
- Being tested
- Thymoglobulin, Bortezomib, Tacrolimus
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Graft vs Host Disease, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinBiological
Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM
Given IV
BortezomibDrug
Also called LDP 341, MLN341, PS-341, PS341
Given IV
TacrolimusDrug
Also called FK 506, Fujimycin, Hecoria, Prograf
Given IV and PO
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus, bortezomib, thymoglobulin | Experimental | Patients receive tacrolimus IV on day -3 through day 180. Patients may receive tacrolimus PO later at the doctor's discretion. Patients receive thymoglobulin IV on days -3, -2, and -1 and bortezomib IV on day 0 and day 3. Patients undergo allogeneic bone marrow transplant on day 0. Receives: Biological: Thymoglobulin; Drug: Bortezomib; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Serious Adverse Events and Adverse Events Related to This Immunosuppressive Regimen
An adverse event (AE) is defined as any untoward medical experience or change of an existing condition that occurs during or after treatment. All AEs occurring during this study, whether observed by the physician, nurse, or reported by the patient, will be graded per NCI CTCAE version 4.0 and recorded on protocol-specific case report forms. A serious adverse event (SAE) is defined as any expected or unexpected adverse event (AE, generally equivalent to CTCAE grades 3, 4 or 5) that results in any of the following outcomes:
- Death
- Life-threatening event
- In-patient hospitalization (not required as part of the treatment) or prolongation of existing hospitalization
- Persistent or significant disability/incapacity
- Congenital anomaly/birth defect
- Cancer
- Overdose
Measured: Up to 6 months post-transplant
Number of Patients Alive and Free of Severe Acute GVHD Following HLA Matched Related or Unrelated Donor Hematopoietic Peripheral Blood Transplant
Will use patient counts for the number of patients alive and free of severe acute graft versus host disease (GVHD) following human leukocyte antigen (HLA) matched related or unrelated donor hematopoietic peripheral blood transplant.
Measured: At 6 months post-transplant
Secondary outcomes (3)
Cumulative Incidence of Grade III-IV aGVHD
Will be summarized as percentage and 95% confidence level will be also constructed.
Measured: Up to 2 years post-transplant
Incidence of Chronic GVHD
Will be summarized as percentage and 95% confidence level will be also constructed.
Measured: Up to 2 years post-transplant
Overall Survival
Will be analyzed with Kaplan Meier method and Logrank test.
Measured: At 1 year post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2016 (estimated)
- Study startSep 2016
- Primary completionJul 2017
- Study completionJul 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 Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by Emory 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zaid Al-Kadhimi, Emory University
- Investigators
- Zaid Al-Kadhimi, MD, Principal investigator, Emory University/Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02877082
- Sponsor's protocol ID
- IRB00082499
- Other IDs
- NCI-2016-01035, Winship3258-16
- Status last verified
- Mar 2018
- First submitted
- 19 Aug 2016
- Last updated
- 30 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Low Toxicity GVHD Prevention and Enhanced Immune Recovery With Tacrolimus, Bortezomib and Thymoglobulin® TBT
- ClinicalTrials.gov ID
- NCT02877082
- Acronym / sponsor ID
- IRB00082499
- Conditions
- Acute Leukemia, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Graft Versus Host Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- Jul 2017 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 24 Aug 2016 (estimated)
- Results
- Posted 30 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well tacrolimus, bortezomib, and anti-thymocyte globulin (thymoglobulin) work in preventing low toxicity graft versus host disease (GVHD) in patients with blood cancer who are undergoing donor stem cell transplant. Tacrolimus and anti-thymocyte globulin may reduce the risk of the recipient's body rejecting the transplant by suppressing the recipient's immune system. Giving bortezomib after the transplant may help prevent GVHD by stopping the donor's cells from attacking the recipient. Giving tacrolimus, bortezomib, and anti-thymocyte globulin may be a better way to prevent low toxicity GVHD in patients with blood cancer undergoing donor stem cell transplant.
Detailed description
PRIMARY OBJECTIVES:
- To determine a composite end point of alive and severe acute GVHD free at 6 months following human leukocyte antigen (HLA) matched related or unrelated donor hematopoietic peripheral blood transplant in patients with hematologic malignancies who receive the immunosuppressive combination tacrolimus, bortezomib, anti-thymocyte globulin (TBT) as GVHD prophylaxis.
II. To determine the safety of this combination in the first six months post-transplant.
SECONDARY OBJECTIVES:
- To determine the cumulative incidence of grade III-IV aGVHD.
II. To determine incidence and severity of chronic GVHD.
III. To determine disease relapse or progression overall and disease free survival at one year.
OUTLINE:
Patients receive tacrolimus intravenously (IV) on day -3 through day 180. Patients may receive tacrolimus orally (PO) later at the doctor's discretion. Patients receive anti-thymocyte globulin IV on days -3, -2, and -1 and bortezomib IV on day 0 and day 3. Patients undergo allogeneic bone marrow transplant on day 0.
After completion of study treatment, patients are followed up for 6 months and then periodically for up to 2 years.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus, bortezomib, thymoglobulin | Experimental | Biological: Thymoglobulin, Drug: Bortezomib, Drug: TacrolimusPatients receive tacrolimus IV on day -3 through day 180. Patients may receive tacrolimus PO later at the doctor's discretion. Patients receive thymoglobulin IV on days -3, -2, and -1 and bortezomib IV on day 0 and day 3. Patients undergo allogeneic bone marrow transplant on day 0. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disorder and myelodysplasia with no circulating blasts and with less than 5% blasts in the bone marrow within 4 weeks of the start of transplant conditioning regimen
- Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma; follicular, marginal zone, diffuse large B-cell or mantle cell lymphoma with chemo-sensitive disease at time of transplant
- Patients must have a related or unrelated peripheral blood stem cell donor; sibling donor must be a 6/6 match for human leukocyte antigen (HLA)-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation; unrelated donor must be 8/8 match at HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing; unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to National Marrow Donor Program (NMDP) criteria
- Cardiac function: ejection fraction > 40%
- Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
Key exclusion criteria (13 listed)
- Prior allogeneic transplant
- Karnofsky performance score < 70%
- Active central nervous system (CNS) involvement by malignant cells
- Patients with uncontrolled bacterial, viral, or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
- Patients with transformed lymphoma (e.g., Richter's transformation arising in follicular lymphoma or chronic lymphocytic leukemia)
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: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAMGiven IV | Biological | Tacrolimus, bortezomib, thymoglobulin |
| BortezomibAlso: LDP 341, MLN341, PS-341, PS341Given IV | Drug | Tacrolimus, bortezomib, thymoglobulin |
| TacrolimusAlso: FK 506, Fujimycin, Hecoria, PrografGiven IV and PO | Drug | Tacrolimus, bortezomib, thymoglobulin |
Primary outcome
Total Number of Serious Adverse Events and Adverse Events Related to This Immunosuppressive Regimen
Time frame: Up to 6 months post-transplant
An adverse event (AE) is defined as any untoward medical experience or change of an existing condition that occurs during or after treatment. All AEs occurring during this study, whether observed by the physician, nurse, or reported by the patient, will be graded per NCI CTCAE version 4.0 and recorded on protocol-specific case report forms. A serious adverse event (SAE) is defined as any expected or unexpected adverse event (AE, generally equivalent to CTCAE grades 3, 4 or 5) that results in any of the following outcomes: * Death * Life-threatening event * In-patient hospitalization (not required as part of the treatment) or prolongation of existing hospitalization * Persistent or significant disability/incapacity * Congenital anomaly/birth defect * Cancer * Overdose
Number of Patients Alive and Free of Severe Acute GVHD Following HLA Matched Related or Unrelated Donor Hematopoietic Peripheral Blood Transplant
Time frame: At 6 months post-transplant
Will use patient counts for the number of patients alive and free of severe acute graft versus host disease (GVHD) following human leukocyte antigen (HLA) matched related or unrelated donor hematopoietic peripheral blood transplant.
3 secondary outcomes
Cumulative Incidence of Grade III-IV aGVHD
Time frame: Up to 2 years post-transplant
Incidence of Chronic GVHD
Time frame: Up to 2 years post-transplant
Overall Survival
Time frame: At 1 year post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Zaid Al-Kadhimi, MD principal investigator
Emory University/Winship 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 Thymoglobulin, Bortezomib and Tacrolimus in people with Acute Leukemia and Chronic Lymphocytic Leukemia, run by Emory 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 11 inclusion and 13 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 30 Apr 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 30 Apr 2018). 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?
Total Number of Serious Adverse Events and Adverse Events Related to This Immunosuppressive Regimen (time frame: Up to 6 months post-transplant). The study lists 2 primary outcomes in all. 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 30 Apr 2018.