Graft Versus Host DiseasePhase 3NCT02178683
Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression
A Phase 3 study testing Tacrolimus and MMF. in people with Graft Versus Host Disease, run by Colorado Blood Cancer Institute at 1 site in United States.
Trial summary
This protocol will evaluate Tacrolimus and MMF after conditioning with fludarabine and low-dose TBI in patients who are not candidates for conventional allografting. A novel approach to immunosuppression will be tested incorporating an early but extended taper of Tacrolimus starting on day +80 or in the case of… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- Tacrolimus and MMF.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Dec 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 AML, ALL, CML, CLL, myelodysplastic syndrome (MDS), NHL, Hodgkin's disease (HD), paroxysmal nocturnal hemoglobinuria (PNH), hypoproliferative dysplasia with or without increased blasts, or myeloma, who are at significantly higher than usual risk for mortality from conventional myeloablative allogeneic SCT due to age or comorbidities:
- Age ≥ to 50 years with AML or ALL in complete remission or with <18% blasts in bone marrow
- Age ≥ to 50 years with MDS or CML.
- Age 16 to 75 years with lymphomas or myeloma, who have failed chemotherapy and are not candidates for an autologous transplant, or who have failed a prior autologous SCT.
- Patients of any age with CLL or low-grade NHL. Patients with CLL and low-grade NHL need to have failed at least first-line treatment, with an alkylating agent, fludarabine or 2-chlorodeoxyadenosine (2-CDA), or anti-CD20 monoclonal antibody rituximab.
- Patients of any age with marrow failure
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- Patients ≥60 years old will first be considered for an allogeneic stem cell transplant from a family member and will be offered an unrelated donor transplant only if no suitable family member, preferably an HLA-matched sibling, is available.
- Patients with hematological malignancy relapsed after prior auto transplantation.
- Patients at high-risk (>60%) of relapsing after autologous transplantation for hematological malignancies may receive allogeneic transplant as "consolidative immunotherapy". Diagnoses include MM, non-HL, HL, AML, ALL and MDS. Minimal duration between auto and allo transplants is 4 weeks.
- Patients of any age with hematologic malignancies treatable by allo SCT, who, because of pre-existing medical conditions or the disease itself (Fanconi anemia or PNH), are considered to be at significantly increased risk for transplant toxicity using high-dose transplantation regimens.
- Patients with metastatic renal cell carcinoma. Must have include good performance status (Karnofsky score ≥ 60%), no active brain metastases, life expectancy of at least 6 months, absence of bulky liver metastases. Patients will be treated on other active disease-specific protocols when available.
- Patients with other malignant diseases treatable with allogeneic SCT may be eligible for this protocol on a case by case basis, if approved by the principal investigator and the BMT attending physicians group.
- Available HLA-identical, a one-antigen mis-matched sibling donor, a phenotypically HLA-matched family member, a phenotypically matched unrelated donor, or a 9/10 matched unrelated donor.
- Age ≤ 75 years.
Who cannot join
- Patients with hematological malignancies eligible for a curative autologous SCT: intermediate- or high-grade NHL with chemo-sensitive first relapse.
- HD with chemo-sensitive first relapse.
- Otherwise healthy patients who are eligible for a conventional myeloablative allogeneic SCT.
- Patients with rapidly progressive intermediate or high-grade NHL, unless in minimal disease state after the last treatment.
- Patients with active uncontrolled CNS involvement with malignancy.
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment.
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- Females who are pregnant.
- Patients who are HIV positive
- Organ dysfunction
- Left ventricle ejection fraction < 35%.
- DLCO <35% of predicted, or receiving continuous supplementary oxygen.
- Liver function tests: total bilirubin >2x the upper limit of normal, and/or transaminases >4x the upper limit of normal.
- Karnofsky score <50 for patients < 60 years, or <70 for patients aged 60 - 69 years
- Creatinine clearance < 60 ml/min.
- Patients with hypertension that is poorly controlled on antihypertensive therapy.
- Patients with a positive PRA or anti-donor T or B cell (+) will be considered for this treatment protocol only if no other option is available.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Juli B Murphy, 720-754-4890, Juli.Murphy@healthonecares.com
Mark Brunvand, MD, 720-754-4800, Mark.Brunvand@healthonecares.com
About this study
Official title: Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression After Conditioning With Fludarabine and Low-Dose Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor HCT
This protocol will evaluate Tacrolimus and MMF after conditioning with fludarabine and low-dose TBI in patients who are not candidates for conventional allografting. A novel approach to immunosuppression will be tested incorporating an early but extended taper of Tacrolimus starting on day +80 or in the case of relapse. The goal is to induce early immunity and GVT effects without compromising GVHD control. The anti-metabolite MMF will be re-introduced on day +100 to try and induce tolerance and block chronic GVHD during the taper of the Tacrolimus. DLI may be given in the presence of disease progression but not for mixed chimerism as in previous protocols.
Read the detailed description
OBJECTIVES
Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients receiving a non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF.
- To evaluate the incidence of grade II-IV GVHD associated with this treatment.
- To evaluate the engraftment when donors who are not HLA-identical family members are utilized for allogeneic stem cell transplantation.
- To evaluate the incidence of GVHD using three times per day MMF after unrelated donor stem cell transplants or two times per day MMF after family donor stem cell transplant.
Minor Objectives A. To evaluate the incidence of chronic GVHD utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors.
- To evaluate disease responses and survival after Flu/TBI allogeneic SCT.
- Conditions
- Graft Versus Host Disease
- Being tested
- Tacrolimus and MMF.
- Keywords
- TACROLIMUS, MYCOPHENOLATE MOFETIL, FLUDARABINE, HLA-MATCHED, MIS-MATCHED
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus and MMF.Drug
Also called Cellcept, MYCOPHENOLATE MOFETIL
First dose of Tacrolimus is given day -4, this continues through day +365. First dose of MMF is given within 4 hours of stem cell infusion, this continues through day +365.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus and Mycophenolate Mofetil | No intervention | Non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family onor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF. Receives: Drug: Tacrolimus and MMF. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment
To measure safe, stable engraftment using Tacrolimus and Mycophenolate Mofetil as post-grafting immunosuppression in patients following conditioning with fludarabine and total-body irradiation for allogeneic stem cell transplant.
Measured: Post 100 days
Secondary outcomes (1)
Graft Versus Host Disease
To measure the incidence of grade II-IV GVHD associated with Tacrolimus and Mycophenolate Mofetil as post-grafting immunosuppression.
Measured: Post 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2014 (estimated)
- Study startNov 2010
- Primary completionDec 2016 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Colorado Blood Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter McSweeney, M.D., Colorado Blood Cancer Institute
- Investigators
- Mark W Brunvand, MD, Principal investigator, Colorado Blood Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02178683
- Sponsor's protocol ID
- CBCI-157
- Status last verified
- Jun 2014
- First submitted
- 16 May 2014
- Last updated
- 1 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tacrolimus and Mycophenolate Mofetil as Post-Grafting Immunosuppression After Conditioning With Fludarabine and Low-Dose Total Body Irradiation for Recipients of HLA-Matched or Mis-Matched Family or Unrelated Donor HCT
- ClinicalTrials.gov ID
- NCT02178683
- Acronym / sponsor ID
- CBCI-157
- Conditions
- Graft Versus Host Disease
- Keywords
- TACROLIMUS, MYCOPHENOLATE MOFETIL, FLUDARABINE, HLA-MATCHED, MIS-MATCHED
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Colorado Blood Cancer InstituteUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 1 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol will evaluate Tacrolimus and MMF after conditioning with fludarabine and low-dose TBI in patients who are not candidates for conventional allografting. A novel approach to immunosuppression will be tested incorporating an early but extended taper of Tacrolimus starting on day +80 or in the case of relapse. The goal is to induce early immunity and GVT effects without compromising GVHD control. The anti-metabolite MMF will be re-introduced on day +100 to try and induce tolerance and block chronic GVHD during the taper of the Tacrolimus. DLI may be given in the presence of disease progression but not for mixed chimerism as in previous protocols.
Detailed description
OBJECTIVES
Major Objectives A. To determine whether stable allogeneic hematopoietic engraftment can be safely established in patients receiving a non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family donor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF.
- To evaluate the incidence of grade II-IV GVHD associated with this treatment.
- To evaluate the engraftment when donors who are not HLA-identical family members are utilized for allogeneic stem cell transplantation.
- To evaluate the incidence of GVHD using three times per day MMF after unrelated donor stem cell transplants or two times per day MMF after family donor stem cell transplant.
Minor Objectives A. To evaluate the incidence of chronic GVHD utilizing Tac/MMF with peripheral blood stem cells from matched or mis-matched allogeneic donors.
- To evaluate disease responses and survival after Flu/TBI allogeneic SCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus and Mycophenolate Mofetil | No intervention | Drug: Tacrolimus and MMF.Non-myeloablative allogeneic SCT from an HLA-Identical or non-identical family onor or unrelated donors, with fludarabine and low-dose TBI, with immunosuppression utilizing tacrolimus and MMF. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with AML, ALL, CML, CLL, myelodysplastic syndrome (MDS), NHL, Hodgkin's disease (HD), paroxysmal nocturnal hemoglobinuria (PNH), hypoproliferative dysplasia with or without increased blasts, or myeloma, who are at significantly higher than usual risk for mortality from conventional myeloablative allogeneic SCT due to age or comorbidities:
- Age ≥ to 50 years with AML or ALL in complete remission or with <18% blasts in bone marrow
- Age ≥ to 50 years with MDS or CML.
- Age 16 to 75 years with lymphomas or myeloma, who have failed chemotherapy and are not candidates for an autologous transplant, or who have failed a prior autologous SCT.
- Patients of any age with CLL or low-grade NHL. Patients with CLL and low-grade NHL need to have failed at least first-line treatment, with an alkylating agent, fludarabine or 2-chlorodeoxyadenosine (2-CDA), or anti-CD20 monoclonal antibody rituximab.
Key exclusion criteria (16 listed)
- Patients with hematological malignancies eligible for a curative autologous SCT: intermediate- or high-grade NHL with chemo-sensitive first relapse.
- HD with chemo-sensitive first relapse.
- Otherwise healthy patients who are eligible for a conventional myeloablative allogeneic SCT.
- Patients with rapidly progressive intermediate or high-grade NHL, unless in minimal disease state after the last treatment.
- Patients with active uncontrolled CNS involvement with malignancy.
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 |
|---|---|---|
| Tacrolimus and MMF.Also: Cellcept, MYCOPHENOLATE MOFETILFirst dose of Tacrolimus is given day -4, this continues through day +365. First dose of MMF is given within 4 hours of stem cell infusion, this continues through day +365. | Drug | Tacrolimus and Mycophenolate Mofetil |
Primary outcome
Engraftment
Time frame: Post 100 days
To measure safe, stable engraftment using Tacrolimus and Mycophenolate Mofetil as post-grafting immunosuppression in patients following conditioning with fludarabine and total-body irradiation for allogeneic stem cell transplant.
1 secondary outcome
Graft Versus Host Disease
Time frame: Post 100 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2014.
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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.
Mark W Brunvand, MD principal investigator
Colorado Blood 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 3 study testing Tacrolimus and MMF. in people with Graft Versus Host Disease, run by Colorado Blood 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 14 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 1 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juli Murphy (720-754-4890, Juli.Murphy@healthonecares.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engraftment (time frame: Post 100 days). 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 1 Jul 2014.