Hematological MalignanciesPhase 1NCT02611063
Evaluation of Fostamatinib in Patients With cGVHD After Allogeneic Stem Cell Transplant
A Phase 1 study testing fostamatinib in people with Hematological Malignancies, run by Stefanie Sarantopoulos, MD, PhD. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate whether fostamatinib, a drug that blocks activated B cells will be effective in preventing and treating chronic graft vs host disease (cGVHD) after allogeneic stem cell transplant. Activated B cells may play a role in development of cGVHD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancies
- What is being tested?
- fostamatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 22 Feb 2022
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who have undergone allogeneic stem cell transplantation for the treatment of any hematological malignancy are eligible. Transplant must have occurred 90 days before the start of study drug.
- Peripheral blood stem cells must have been used as the stem cell source.
- Patients must have received transplantation from adult donors (both related and unrelated) who are Human Leukocyte Antigen (HLA) matched or mismatched at 1 locus (5/6) or are mismatched at one allele (3/6). Class I and II typing is to be performed by standard methods at our institution.
- Complete remission of hematological malignancy prior to transplantation. All patients must have undergone appropriate staging for their malignancy prior to transplantation including bone marrow aspirate/biopsy and radiographic scanning if indicated.
- Patients who have undergone a non-myeloablative stem cell transplant must have > 65% donor lymphoid hematopoiesis within 30 days of study enrollment.
- Patient age greater than 18 years of age.
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- ECOG performance status 0-2 or Karnofsky Performance Status (KPS) > 60.
- Must be able to tolerate routine oral posaconazole or voriconazole as fungal prophylaxis therapy.
- Written informed consent.
Who cannot join
- Recipients of allogeneic stem cell transplantation using a single or multiple umbilical cord blood units or using bone marrow.
- Participation in a clinical trial evaluating another preventative strategy for chronic GVHD or ongoing participation in a clinical trial for therapy of acute GVHD. Prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used > 14 days prior to enrollment.
- Evidence of relapsed hematologic malignancy based on routine restaging studies.
- Evidence of any active uncontrolled infection (bacterial, viral or fungal) or evidence of natural exposure to Hepatitis B, Hepatitis C or HIV without demonstration of PCR negativity for said virus. Vaccination to Hepatitis B is not an exclusion criterion.
- Any evidence of ongoing gastrointestinal or hepatic acute GVHD or evidence of greater than ongoing Stage I cutaneous acute GVHD at time of enrollment. Ongoing, tapering therapy for resolved acute GVHD is permissible.
- Patients with GVHD with chronic features diagnosed prior to day +60 or prior to enrollment are ineligible.
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- Patients may have received no more than one Donor Lymphocyte Infusion (DLI), DLI must have been administered > 6 weeks prior to enrollment on study, and no plans for a DLI in the upcoming 30 days.
- Any major cardiovascular even within 6 months of study initiation, including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, heart failure uncontrolled by medications or New York Heart Association Class III or IV heart failure.
- Uncontrolled or poorly controlled hypertension, defined as systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg, whether or not the subject is receiving anti-hypertensive treatment. Subjects may be rescreened if the blood pressure is successfully and promptly controlled within 5 days using conventional anti-hypertensive therapy to achieve optimal blood pressure control (<140/90 mmHg).
- Active hemolytic anemia.
- History of arterial or venous thrombosis (unless a single episode of venous thrombosis > 1 year prior to study initiation).
- Liver function test abnormalities including ALT or AST > 3.0x ULN; total bilirubin > 1.5x ULN; alkaline phosphatase > 2.5 x ULN
- Neutrophil count < 1.5 x 10e9/L or platelet count < 75 x10e9/L
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University of Medicine
Durham, North Carolina, 27710
About this study
Official title: A Phase I Trial of Fostamatinib and Chronic Graft vs. Host Disease Development After Allogeneic Stem Cell Transplantation
The purpose of this study is to evaluate whether fostamatinib, a drug that blocks activated B cells will be effective in preventing and treating chronic graft vs host disease (cGVHD) after allogeneic stem cell transplant. Activated B cells may play a role in development of cGVHD. Inhibiting the B cell activation using fostamatinib after allogeneic stem cell transplant may prevent the development of cGVHD.
Read the detailed description
Design \& Procedures
All patients will undergo allogeneic stem cell transplantation (HCT) according to the program's standards. No specific conditioning regimen is mandated. The stem cell source must have been peripheral blood stem cells. Prophylaxis against acute GVHD must be with standard agents (sirolimus and/or tacrolimus and/or methotrexate and/or cyclosporine). Participation in a trial evaluating novel agents for therapy of acute GVHD is allowed, as long as the experimental agent was discontinued > 14 days prior to trial entry.
Therapy: Patients will receive 100mg daily, 150mg daily or 100 mg bid beginning 90 days after allogeneic transplantation and continue for up to 1 year from day of transplant OR beginning at time of steroid-refractory cGVHD. Dosage will be determined using the modified continual reassessment method.
Patient evaluations: Patients will be evaluated for cGVHD and other toxicity at a minimum on day 1(baseline), day 3, day 11, day 25, day 39, day 60, day 88, day 116, day 144, day 186, day 228, and day 275 from initiation of protocol therapy. While the assessment for safety is determined based on the evaluation at day 60, patients may stay on therapy for up to 1 year after transplantation (study treatment day 275). In addition, patients will be observed for one year after stopping study treatment with evaluation for toxicity and cGVHD during clinic visits at 6 and 12 months after completion of study therapy. If at any time within the first year after transplantation, a study subject is determined to have evidence of moderate or severe stage cGVHD according to NIH consensus criteria for global severity, the subject will be removed from this clinical trial and appropriate therapy for cGVHD will be administered per the treating physician's discretion. The study subject may continue to receive Fostamatinib as per the guidelines of this clinical trial in the event that mild stage cGVHD is diagnosed. If cGVHD develops during the observation period, a second course of Fostamatinib at 100% tolerated study dose may be given during the observation period.
Immunosuppressive and other medications should be tapered according to the treating physicians' discretion with careful attention to the clinical trial or treatment plan to which the participating subject is already enrolled.
Laboratory samples will be obtained according to the study schedule. The following tests are to be collected and analyzed for the study: complete blood counts, serum chemistry, liver function tests (LFTs), chimerism analysis if indicated, and immunology/correlative science studies.
This study will be open to members of all demographic groups who meet the eligibility criteria. Approximately 18 subjects will be recruited at Duke.
A total of eighteen patients will receive fostamatinib beginning at day 90 after allogeneic transplantation. The safety assessment is determined at day 60. Patients with steroid-refractory cGVHD are also eligible for this phase I study. Three dose levels are considered: 100 mg qd, 150 mg qd, 100 mg bid, and the target dose-limiting toxicity (DLT) probability is 0.33. The Bayesian model averaging continual reassessment method (BMA-CRM) will be used for this trial.[15]
The investigators will study targeted molecular mechanisms underpinning aberrant B-cell signaling in cGVHD. Corollary studies will determine whether B and T cell subsets and/or soluble B-cell activation factors are altered after Syk inhibition. The objective is to implement preemptive targeted therapies that decrease excessive immune activation in patients.
- Conditions
- Hematological Malignancies
- Being tested
- fostamatinib
- Keywords
- allogeneic stem cell transplant
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fostamatinibDrug
100mg qd, 150mg qd, or 100mg bid
| Study group | Role | What they receive |
|---|---|---|
| fostamatinib | Experimental | Subjects will receive fostamatinib 100 mg qd, 150 mg qd, or 100 mg bid with dosage determined by the modified continual reassessment method. The treatment period begins at baseline 90 days after transplant and continues for up to 1 year after transplant. In patients with steroid-refractory cGVHD who are also included on this study, these subjects also receive fostamatinib 100mg qd, 150mg qd, or 100mg bid dosage determined by the modified continual reassessment method. Receives: Drug: fostamatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate maximum tolerated dose of fostamatinib delivered following allogenic transplantation
three dose levels are considered: 100 mg qd, 150 mg qd, 100 mg bid dose limiting toxicity is any of the following
- Grade > or = II aGVHD of the gut or liver or Grade III aGVHD of the skin lasting > 7 days and related to the agent
- Grade 3 toxicity from the agent in the cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary or neurologic categories that lasts > 5 days
- fostamatinib related mortality (TRM)
- absolute neutrophil count (ANC) of Grade 3 or 4 plus fever attributable to the agent
- ANC<0.5 x 10e9/L for >5 days and attributable to the agent
- platelet < 25 x 10e 9/L and attributable to the agent
Measured: day 60 after fostamatinib initiation
Secondary outcomes (5)
Incidence of chronic graft vs host disease (cGVHD)
Measured: one and two years when fostamatinib administered after allogeneic HCT
Incidence of relapse of chronic graft vs host disease (cGVHD)
Measured: one and two years when fostamatinib administered after allogeneic HCT
B-cell activation rate
B-cell activation rate before and after fostamatinib administration
Measured: two years
B-cell death rate
B-cell death rate before and after fostamatinib administration
Measured: two years
Number of B-cells
Immune recovery as measured by the number of B-cells before and after fostamatinib administration
Measured: two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study startJan 2016
- Primary completionFeb 2021
- Study completion22 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignanciesStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stefanie Sarantopoulos, MD, PhD.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Stefanie Sarantopoulos, MD, PhD., Duke University
- Investigators
- Stefanie Sarantopoulos, MD, PhD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02611063
- Sponsor's protocol ID
- Pro00064227
- Status last verified
- Mar 2023
- First submitted
- 16 Nov 2015
- Last updated
- 17 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Fostamatinib and Chronic Graft vs. Host Disease Development After Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT02611063
- Acronym / sponsor ID
- Pro00064227
- Conditions
- Hematological Malignancies
- Keywords
- allogeneic stem cell transplant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Stefanie Sarantopoulos, MD, PhD.University, hospital or other
- Study start
- Jan 2016
- Primary completion
- Feb 2021 (actual)
- Study completion
- 22 Feb 2022 (actual)
- First posted
- 20 Nov 2015 (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.
The purpose of this study is to evaluate whether fostamatinib, a drug that blocks activated B cells will be effective in preventing and treating chronic graft vs host disease (cGVHD) after allogeneic stem cell transplant. Activated B cells may play a role in development of cGVHD. Inhibiting the B cell activation using fostamatinib after allogeneic stem cell transplant may prevent the development of cGVHD.
Detailed description
Design \& Procedures
All patients will undergo allogeneic stem cell transplantation (HCT) according to the program's standards. No specific conditioning regimen is mandated. The stem cell source must have been peripheral blood stem cells. Prophylaxis against acute GVHD must be with standard agents (sirolimus and/or tacrolimus and/or methotrexate and/or cyclosporine). Participation in a trial evaluating novel agents for therapy of acute GVHD is allowed, as long as the experimental agent was discontinued > 14 days prior to trial entry.
Therapy: Patients will receive 100mg daily, 150mg daily or 100 mg bid beginning 90 days after allogeneic transplantation and continue for up to 1 year from day of transplant OR beginning at time of steroid-refractory cGVHD. Dosage will be determined using the modified continual reassessment method.
Patient evaluations: Patients will be evaluated for cGVHD and other toxicity at a minimum on day 1(baseline), day 3, day 11, day 25, day 39, day 60, day 88, day 116, day 144, day 186, day 228, and day 275 from initiation of protocol therapy. While the assessment for safety is determined based on the evaluation at day 60, patients may stay on therapy for up to 1 year after transplantation (study treatment day 275). In addition, patients will be observed for one year after stopping study treatment with evaluation for toxicity and cGVHD during clinic visits at 6 and 12 months after completion of study therapy. If at any time within the first year after transplantation, a study subject is determined to have evidence of moderate or severe stage cGVHD according to NIH consensus criteria for global severity, the subject will be removed from this clinical trial and appropriate therapy for cGVHD will be administered per the treating physician's discretion. The study subject may continue to receive Fostamatinib as per the guidelines of this clinical trial in the event that mild stage cGVHD is diagnosed. If cGVHD develops during the observation period, a second course of Fostamatinib at 100% tolerated study dose may be given during the observation period.
Immunosuppressive and other medications should be tapered according to the treating physicians' discretion with careful attention to the clinical trial or treatment plan to which the participating subject is already enrolled.
Laboratory samples will be obtained according to the study schedule. The following tests are to be collected and analyzed for the study: complete blood counts, serum chemistry, liver function tests (LFTs), chimerism analysis if indicated, and immunology/correlative science studies.
This study will be open to members of all demographic groups who meet the eligibility criteria. Approximately 18 subjects will be recruited at Duke.
A total of eighteen patients will receive fostamatinib beginning at day 90 after allogeneic transplantation. The safety assessment is determined at day 60. Patients with steroid-refractory cGVHD are also eligible for this phase I study. Three dose levels are considered: 100 mg qd, 150 mg qd, 100 mg bid, and the target dose-limiting toxicity (DLT) probability is 0.33. The Bayesian model averaging continual reassessment method (BMA-CRM) will be used for this trial.[15]
The investigators will study targeted molecular mechanisms underpinning aberrant B-cell signaling in cGVHD. Corollary studies will determine whether B and T cell subsets and/or soluble B-cell activation factors are altered after Syk inhibition. The objective is to implement preemptive targeted therapies that decrease excessive immune activation in patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| fostamatinib | Experimental | Drug: fostamatinibSubjects will receive fostamatinib 100 mg qd, 150 mg qd, or 100 mg bid with dosage determined by the modified continual reassessment method. The treatment period begins at baseline 90 days after transplant and continues for up to 1 year after transplant. In patients with steroid-refractory cGVHD who are also included on this study, these subjects also receive fostamatinib 100mg qd, 150mg qd, or 100mg bid dosage determined by the modified continual reassessment method. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients who have undergone allogeneic stem cell transplantation for the treatment of any hematological malignancy are eligible. Transplant must have occurred 90 days before the start of study drug.
- Peripheral blood stem cells must have been used as the stem cell source.
- Patients must have received transplantation from adult donors (both related and unrelated) who are Human Leukocyte Antigen (HLA) matched or mismatched at 1 locus (5/6) or are mismatched at one allele (3/6). Class I and II typing is to be performed by standard methods at our institution.
- Complete remission of hematological malignancy prior to transplantation. All patients must have undergone appropriate staging for their malignancy prior to transplantation including bone marrow aspirate/biopsy and radiographic scanning if indicated.
- Patients who have undergone a non-myeloablative stem cell transplant must have > 65% donor lymphoid hematopoiesis within 30 days of study enrollment.
Key exclusion criteria (14 listed)
- Recipients of allogeneic stem cell transplantation using a single or multiple umbilical cord blood units or using bone marrow.
- Participation in a clinical trial evaluating another preventative strategy for chronic GVHD or ongoing participation in a clinical trial for therapy of acute GVHD. Prior completion of experimental therapy for acute GVHD is permissible if the experimental agent was used > 14 days prior to enrollment.
- Evidence of relapsed hematologic malignancy based on routine restaging studies.
- Evidence of any active uncontrolled infection (bacterial, viral or fungal) or evidence of natural exposure to Hepatitis B, Hepatitis C or HIV without demonstration of PCR negativity for said virus. Vaccination to Hepatitis B is not an exclusion criterion.
- Any evidence of ongoing gastrointestinal or hepatic acute GVHD or evidence of greater than ongoing Stage I cutaneous acute GVHD at time of enrollment. Ongoing, tapering therapy for resolved acute GVHD is permissible.
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 |
|---|---|---|
| fostamatinib100mg qd, 150mg qd, or 100mg bid | Drug | fostamatinib |
Primary outcome
Evaluate maximum tolerated dose of fostamatinib delivered following allogenic transplantation
Time frame: day 60 after fostamatinib initiation
three dose levels are considered: 100 mg qd, 150 mg qd, 100 mg bid dose limiting toxicity is any of the following 1. Grade > or = II aGVHD of the gut or liver or Grade III aGVHD of the skin lasting > 7 days and related to the agent 2. Grade 3 toxicity from the agent in the cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary or neurologic categories that lasts > 5 days 3. fostamatinib related mortality (TRM) 4. absolute neutrophil count (ANC) of Grade 3 or 4 plus fever attributable to the agent 5. ANC<0.5 x 10e9/L for >5 days and attributable to the agent 6. platelet < 25 x 10e 9/L and attributable to the agent
5 secondary outcomes
Incidence of chronic graft vs host disease (cGVHD)
Time frame: one and two years when fostamatinib administered after allogeneic HCT
Incidence of relapse of chronic graft vs host disease (cGVHD)
Time frame: one and two years when fostamatinib administered after allogeneic HCT
B-cell activation rate
Time frame: two years
B-cell death rate
Time frame: two years
Number of B-cells
Time frame: two years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
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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.
Stefanie Sarantopoulos, MD, PhD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing fostamatinib in people with Hematological Malignancies, run by Stefanie Sarantopoulos, MD, PhD. 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 14 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 17 Mar 2023. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluate maximum tolerated dose of fostamatinib delivered following allogenic transplantation (time frame: day 60 after fostamatinib initiation). 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 17 Mar 2023.