Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Hematologic Neoplasms

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Phase II Trial to evaluate the efficacy of 200mg fostamatinib

Fostamatinib

Bernadette Weidman, RN, MSN, PMP

This study will evaluate the effectiveness of fostamatinib (200 mg twice a day) in patients with worsening or unmanageable lymphoma with a specific type of lymphoma called Diffuse Large B-Cell Lymphoma (abbreviated as DLBCL)

Phase II Trial to Evaluate the Efficacy of Fostamatinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Study to Learn if 200mg Test Drug (Fostamatinib) Helps People With Large B-Cell Lymphoma,a Type of Blood Cancer

Phase II Trial to Evaluate the Efficacy of Fostamatinib in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma(DLBCL)

Patients were assessed using the revised response criteria for malignant lymphoma (Cheson). Patients were assessed for response, with CT and FDG-PET scans at 8 weeks, then every 12 weeks until radiological progression by clinical CT. Complete response (CR) was defined as disappearance of all target and non-target lesions in the liver and spleen and all lymph node masses regressed to normal size. Partial response (PR) was defined as ≥50% reduction in sum of the product of the diameters (SPD) for measured lymph nodes, splenic and liver lesions separately compared to baseline SPD. Objective response rate (CR + PR) analysis, exact binomial test, primary analysis.

AstraZeneca

100mg BID

200mg BID

Total

Age, Continuous

Sex: Female, Male

Most patients were male (69.1%). The mean age (± standard deviation) was 63.6 ± 12.6 years.

Bernadette Weidman

Full analysis set - all randomised patients

Objective Response Rate

Overall Study

Graft vs Host Disease

Hematologic Diseases

Chronic Graft Versus Host Disease

Homologous Wasting Disease

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.

fostamatinib

Stefanie Sarantopoulos, MD, PhD

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.

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.

Evaluation of Fostamatinib in Patients With cGVHD After Allogeneic Stem Cell Transplant

A Phase I Trial of Fostamatinib and Chronic Graft vs. Host Disease Development After Allogeneic Stem Cell Transplantation

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

B-cell activation rate before and after fostamatinib administration

B-cell death rate before and after fostamatinib administration

Immune recovery as measured by the number of B-cells before and after fostamatinib administration

Stefanie Sarantopoulos, MD, PhD.

Associate Professor of Medicine

Symptoms and General Pathology

Syndrome

Leukemia

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Leukemia, Myelomonocytic, Acute

Bone Marrow Diseases

Precancerous Conditions

Leukemia, Myeloid

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Chronic Disease

Disease Attributes

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Patients receive fostamatinib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles (week 24) in the absence of disease progression or unacceptable toxicity.

Guillermo M. Bravo

Guillermo M Bravo

This phase I trial is to find out the best dose, possible benefits and/or side effects of fostamatinib in treating patients with lower-risk myelodysplastic syndromes or chronic myelomonocytic leukemia who have failed therapy with hypomethylating agents. Fostamatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To assess the safety and tolerability of different doses of fostamatinib in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) as the measure of adverse events (AEs), serious AEs (SAEs), and laboratory abnormalities on fostamatinib treatment and frequency of discontinuation or interruptions of fostamatinib due to fostamatinib related AEs.

SECONDARY OBJECTIVES:

I. To assess overall survival (OS), duration of response, relapse-free survival (RFS).

II. To assess overall response (OR) rate to different dose schedules of fostamatinib in patients with MDS and CMML following International Working Group (IWG) 2006 response criteria.

III. Hematological response at the end of 2 cycles for each dose level. IV. Frequency of dose escalation of fostamatinib to a dose greater than 100 mg twice daily (BID).

V. Frequency of platelet transfusion independence. VI. Frequency of red blood cell (RBC) transfusion independence for \> 8 weeks. VII. Endpoints related to correlative studies.

OUTLINE: This is a dose-escalation study.

Patients receive fostamatinib orally (PO) BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles (week 24) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6 months thereafter.

Fostamatinib for the Treatment of Lower-risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents

Phase I Open-Label Study of Fostamatinib, a SYK Inhibitor, in Patients With Lower-Risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Learn if 200mg Test Drug (Fostamatinib) Helps People With Large B-Cell Lymphoma,a Type of Blood Cancer	NCT01499303	Diffuse Large B...	Fostamatinib	18 Years -	AstraZeneca
Study to Learn if 200mg Test Drug (Fostamatinib) Helps People With Large B-Cell Lymphoma,a Type of Blood Cancer	NCT01499303	Diffuse Large B...	Fostamatinib	18 Years -	AstraZeneca
Evaluation of Fostamatinib in Patients With cGVHD After Allogeneic Stem Cell Transplant	NCT02611063	Hematological M...	fostamatinib	18 Years -	Duke University
Fostamatinib for the Treatment of Lower-risk Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia Who Have Failed Therapy With Hypomethylating Agents	NCT05030675	Refractory Chro... Refractory Myel...	Fostamatinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for fostamatinib

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