Graft-versus-host DiseasePhase 2NCT02799888
Maraviroc-Based GVHD Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Transplantation
A Phase 2 study testing Maraviroc, Cyclosporine (in HLA-Unrelated Donor Transplantation) and Tacrolimus (in HLA-Mismatched Related Donor Transplantation) in people with Graft-versus-host Disease and Hematopoietic Stem Cell Transplantation, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
Trial summary
HLA-mismatched unrelated donor (MMUD) and HLA-haploidentical donor (Haplo Donor) hematopoietic stem cell transplantation (HSCT) is associated with increased graft-versus-host-disease (GVHD) and impaired survival. Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation
- What is being tested?
- Maraviroc, Cyclosporine (in HLA-Unrelated Donor Transplantation) and Tacrolimus (in HLA-Mismatched Related Donor Transplantation)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Apr 2014to Apr 2017
- Phase
- Phase 2
- 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 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 12-65 years (patient is older than 12.0 and less than 66.0 years old)
- Patients with acute leukemia, myelodysplastic syndrome or lymphoma who scheduled to undergo allogeneic stem-cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors
- Renal function: estimated creatinine clearance greater than 40 mL/minute (using the Cockcroft-Gault formula and actual body weight)
- Hepatic function: Baseline direct bilirubin, alanine aminotransferase (ALT) lower than three times the upper limit of normal
- Pulmonary disease: forced vital capacity (FVC) or forced expiratory volume at one second (FEV1) > 40% predicted
- Cardiac ejection fraction > 40%
- Signed informed consent
Who cannot join
- Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
- Prior allogeneic transplant
- Karnofsky Performance Score < 70%
- Patients who are not undergoing standard GVHD prophylaxis with cyclosporine/tacrolimus and methotrexate
- Patients with uncontrolled bacterial, viral or fungal infections
- Patients receiving other investigational drugs for GVHD
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematopoietic Stem Cell Transplantation
Beijing, Beijing Municipality, 100071
About this study
Official title: Safety and Efficacy of Maraviroc-Based Graft-Versus-Host-Disease Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Donor Transplantation
HLA-mismatched unrelated donor (MMUD) and HLA-haploidentical donor (Haplo Donor) hematopoietic stem cell transplantation (HSCT) is associated with increased graft-versus-host-disease (GVHD) and impaired survival. The chemokine receptor 5 (CCR5) antagonist maraviroc has immunomodulatory properties potentially beneficial for GVHD control as it can blockade lymphocyte chemotaxis without impairing T-cell function. The aim of this study is to evaluate the safety and efficacy of maraviroc combined with standard graft-versus-host-disease prophylaxis in patients with hematologic malignancies after allogeneic stem cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors. Based on the results of our previously small sample study with maraviroc combined with cyclosporine/tacrolimus and methotrexate for prophylaxis of GVHD, the investigators plan to perform the clinical trail.
- Being tested
- Maraviroc, Cyclosporine (in HLA-Unrelated Donor Transplantation), Tacrolimus (in HLA-Mismatched Related Donor Transplantation), Methotrexate
- Keywords
- Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation, Acute Leukemia, Myelodysplastic syndrome, Lymphoma
- Medical subject headings
- Graft vs Host Disease, Myelodysplastic Syndromes, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaravirocDrug
Also called Selzentry
Maraviroc will be administered 300mg twice daily and start on day -2 end on day +30 after stem cell transplant for 33 days.
Cyclosporine (in HLA-Unrelated Donor Transplantation)Drug
Also called Sandimmune, Gengraf, Neoral
Cyclosporine will be given intravenously at a dose of 2-3 mg/kg starting Day -1. Subsequent dosing will be based on blood levels. Patients were advanced to oral cyclosporine once they could tolerate. The dose should be adjusted accordingly to maintain a suggested target serum level of 150-250 ng/mL. In the absence of aGVHD, the oral cyclosporine dose was reduced by approximately 5% weekly, beginning on or near day 100, and therapy was usually discontinued by Day 180 after transplantation or relapse.
Tacrolimus (in HLA-Mismatched Related Donor Transplantation)Drug
Also called Prograf®, FK506
Tacrolimus will be given orally at a dose of 0.05 mg/kg twince a day or intravenously at a dose of 0.03 mg/kg starting Day -3. Subsequent dosing should be adjusted accordingly to maintain a suggested target serum level of 5-10 ng/mL. Tacrolimus taper can be initiated at a minimum of 100 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.
MethotrexateDrug
Also called MTX
Methotrexate will be administered intravenously at a dose of 15 mg/m^2 on day +1, and 10 mg/m^2 on day +3, +6 and +11 after HSC transplantation.at the doses of 15 mg/m^2 IV bolus on Day +1, and 10 mg/m^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +11 dose of methotrexate will be not given to those patients who fail to reach white blood cell count (WBC) of more than 1.0×10^9/L.
| Study group | Role | What they receive |
|---|---|---|
| Maraviroc + standard GVHD prophylaxis | Experimental | Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally. Receives: Drug: Maraviroc; Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation); Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation); Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Acute GVHD Grades II-IV
Measured: 1 Year
Secondary outcomes (8)
Incidence of Acute GVHD Grades III-IV
Measured: By day +100 post-HSCT
Incidence of Chronic GVHD
Measured: 1 Year
Hematologic Recovery (Neutrophils and Platelets)
Measured: Up to day +100 post-HSCT
Disease Relapse or Progression
Measured: 1 Year
Incidence of Transplant-Related Mortality
Measured: By day +100 post-HSCT
Frequency of Grade 3 or Greater Toxicities
Measured: Up to day +100 post-HSCT
Incidence of Grade 2 and 3 Infections
Measured: 1 Year
Overall Survival
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 posted15 Jun 2016 (estimated)
- Study startApr 2014
- Primary completionDec 2016 (estimated)
- Study completionApr 2017 (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 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hu Chen, M.D., Ph.D., Principal investigator, Affiliated Hospital to Academy of Military Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02799888
- Sponsor's protocol ID
- 307-maraviroc-001
- Status last verified
- Jun 2016
- First submitted
- 3 Jun 2016
- Last updated
- 15 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Maraviroc-Based Graft-Versus-Host-Disease Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Donor Transplantation
- ClinicalTrials.gov ID
- NCT02799888
- Acronym / sponsor ID
- 307-maraviroc-001
- Keywords
- Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation, Acute Leukemia, Myelodysplastic syndrome, Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Affiliated Hospital to Academy of Military Medical SciencesUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Apr 2017 (estimated)
- First posted
- 15 Jun 2016 (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.
HLA-mismatched unrelated donor (MMUD) and HLA-haploidentical donor (Haplo Donor) hematopoietic stem cell transplantation (HSCT) is associated with increased graft-versus-host-disease (GVHD) and impaired survival. The chemokine receptor 5 (CCR5) antagonist maraviroc has immunomodulatory properties potentially beneficial for GVHD control as it can blockade lymphocyte chemotaxis without impairing T-cell function. The aim of this study is to evaluate the safety and efficacy of maraviroc combined with standard graft-versus-host-disease prophylaxis in patients with hematologic malignancies after allogeneic stem cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors. Based on the results of our previously small sample study with maraviroc combined with cyclosporine/tacrolimus and methotrexate for prophylaxis of GVHD, the investigators plan to perform the clinical trail.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Maraviroc + standard GVHD prophylaxis | Experimental | Drug: Maraviroc, Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation), Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation), Drug: MethotrexateMaraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Age 12-65 years (patient is older than 12.0 and less than 66.0 years old)
- Patients with acute leukemia, myelodysplastic syndrome or lymphoma who scheduled to undergo allogeneic stem-cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors
- Renal function: estimated creatinine clearance greater than 40 mL/minute (using the Cockcroft-Gault formula and actual body weight)
- Hepatic function: Baseline direct bilirubin, alanine aminotransferase (ALT) lower than three times the upper limit of normal
- Pulmonary disease: forced vital capacity (FVC) or forced expiratory volume at one second (FEV1) > 40% predicted
Key exclusion criteria (6 listed)
- Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
- Prior allogeneic transplant
- Karnofsky Performance Score < 70%
- Patients who are not undergoing standard GVHD prophylaxis with cyclosporine/tacrolimus and methotrexate
- Patients with uncontrolled bacterial, viral or fungal infections
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 |
|---|---|---|
| MaravirocAlso: SelzentryMaraviroc will be administered 300mg twice daily and start on day -2 end on day +30 after stem cell transplant for 33 days. | Drug | Maraviroc + standard GVHD prophylaxis |
| Cyclosporine (in HLA-Unrelated Donor Transplantation)Also: Sandimmune, Gengraf, NeoralCyclosporine will be given intravenously at a dose of 2-3 mg/kg starting Day -1. Subsequent dosing will be based on blood levels. Patients were advanced to oral cyclosporine once they could tolerate. The dose should be adjusted accordingly to maintain a suggested target serum level of 150-250 ng/mL. In the absence of aGVHD, the oral cyclosporine dose was reduced by approximately 5% weekly, beginning on or near day 100, and therapy was usually discontinued by Day 180 after transplantation or relapse. | Drug | Maraviroc + standard GVHD prophylaxis |
| Tacrolimus (in HLA-Mismatched Related Donor Transplantation)Also: Prograf®, FK506Tacrolimus will be given orally at a dose of 0.05 mg/kg twince a day or intravenously at a dose of 0.03 mg/kg starting Day -3. Subsequent dosing should be adjusted accordingly to maintain a suggested target serum level of 5-10 ng/mL. Tacrolimus taper can be initiated at a minimum of 100 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD. | Drug | Maraviroc + standard GVHD prophylaxis |
| MethotrexateAlso: MTXMethotrexate will be administered intravenously at a dose of 15 mg/m^2 on day +1, and 10 mg/m^2 on day +3, +6 and +11 after HSC transplantation.at the doses of 15 mg/m^2 IV bolus on Day +1, and 10 mg/m^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +11 dose of methotrexate will be not given to those patients who fail to reach white blood cell count (WBC) of more than 1.0×10^9/L. | Drug | Maraviroc + standard GVHD prophylaxis |
Primary outcome
Incidence of Acute GVHD Grades II-IV
Time frame: 1 Year
8 secondary outcomes
Incidence of Acute GVHD Grades III-IV
Time frame: By day +100 post-HSCT
Incidence of Chronic GVHD
Time frame: 1 Year
Hematologic Recovery (Neutrophils and Platelets)
Time frame: Up to day +100 post-HSCT
Disease Relapse or Progression
Time frame: 1 Year
Incidence of Transplant-Related Mortality
Time frame: By day +100 post-HSCT
Frequency of Grade 3 or Greater Toxicities
Time frame: Up to day +100 post-HSCT
Incidence of Grade 2 and 3 Infections
Time frame: 1 Year
Overall Survival
Time frame: 1 Year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2016.
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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.
Hu Chen, M.D., Ph.D. principal investigator
Affiliated Hospital to Academy of Military Medical Sciences
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 Maraviroc, Cyclosporine (in HLA-Unrelated Donor Transplantation) and Tacrolimus (in HLA-Mismatched Related Donor Transplantation) in people with Graft-versus-host Disease and Hematopoietic Stem Cell Transplantation, run by Affiliated Hospital to Academy of Military Medical Sciences at 1 site in China.
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 7 inclusion and 6 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 15 Jun 2016. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hongmei Ning, M.D., Ph.D. (+86 10 66947405, ninghongmei72@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Acute GVHD Grades II-IV (time frame: 1 Year). 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 15 Jun 2016.