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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01499303
• Collaborator: (none)
• Enrollment: 101
• Locations: 21
• Arm: 1
• Duration (Months): 22
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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)

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: Fostamatinib	Phase 2

Detailed Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 101 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial to Evaluate the Efficacy of Fostamatinib in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma(DLBCL)
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fostamatinib 200 200mg fostamatinib bid n=60	Drug: Fostamatinib; Phase II Trial to evaluate the efficacy of 200mg fostamatinib

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate [Week 8]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Aged at least 18 years of age.

• Patients with relapsed or refractory diffuse large B-cell lymphoma who have previously received R-CHOP (or equivalent) chemo-immunotherapy and high dose chemotherapy with stem cell rescue, or who are ineligible for high dose therapy with stem cell rescue.

• Measurable disease as defined by Cheson et al 2007 criteria.

• One fresh pre-treatment excisional or core needle biopsy from suitable and accessible site.

• World Health Organization (WHO) performance status 0 to 1.

Exclusion Criteria:

• Treatment with nitrosurea, mitomycin C, investigational agents or study drugs w/in28 days of first dose of study treatment, any other chemotherapy, immunotherapy or anticancer agents w/in 3 weeks of first dose of study treatment, previous fostamatinib.

• With the exception of alopecia, any unresolved toxicities from prior therapy or surgery greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.

• Uncontrolled hypertension (defined as >140mmHg systolic and/or > 90 mmHG diastolic at baseline with or without antihypertensive therapy.

• Evidence of tuberculosis (TB).

• Inadequate boen marrow reserve.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Huntsville	Alabama	United States
2	Research Site	Denver	Colorado	United States
3	Research Site	New Haven	Connecticut	United States
4	Research Site	Sarasota	Florida	United States
5	Research Site	Atlanta	Georgia	United States
6	Research Site	Iowa City	Iowa	United States
7	Research Site	Baltimore	Maryland	United States
8	Research Site	Boston	Massachusetts	United States
9	Research Site	Rochester	Minnesota	United States
10	Research Site	St. Louis	Missouri	United States
11	Research Site	Hackensack	New Jersey	United States
12	Research Site	New York	New York	United States
13	Research Site	Rochester	New York	United States
14	Research Site	Columbus	Ohio	United States
15	Research Site	Nashville	Tennessee	United States
16	Research Site	Houston	Texas	United States
17	Research Site	San Antonio	Texas	United States
18	Research Site	Charlottesville	Virginia	United States
19	Research Site	Seattle	Washington	United States
20	Research Site	London		United Kingdom
21	Research Site	Southampton		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Bernadette Weidman, RN, MSN, PMP, Sponsor GmbH

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• D4302C00001_CSR_Synopsis

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01499303
• Other Study ID Numbers: D4302C00001
• First Posted: Dec 26, 2011
• Last Update Posted: Aug 22, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by AstraZeneca: lymphoma; DLBCL; fostamatinib; Diffuse Large B-Cell Lymphoma (DLBCL)
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

Participant Flow

Recruitment Details	This study was conducted in the US and UK. Patient enrolment was completed on 14 June 2013. However three patients, considered by the Investigator to still be receiving clinical benefit, continue to receive fostamatinib. A total of 102 patients were enrolled and 68 received Fostamatinib doses of 100mg or 200mg and 38 Screen Failures.

Arm/Group Title	100mg BID	200mg BID
Arm/Group Description	100mg Fostmatinib BID	200mg Fostmatinib BID
Period Title: Overall Study
STARTED	21	47
COMPLETED	18	40
NOT COMPLETED	3	7

Baseline Characteristics

Arm/Group Title	100mg BID	200mg BID	Total
Arm/Group Description	100mg Fostmatinib BID	200mg Fostmatinib BID	Total of all reporting groups
Overall Participants	21	47	68
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.9 (12.38)	63.9 (12.78)	63.6 (12.57)
Sex: Female, Male (Count of Participants)
Female	9 42.9%	12 25.5%	21 30.9%
Male	12 57.1%	35 74.5%	47 69.1%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate
Description	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.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Full analysis set - all randomised patients

Arm/Group Title	100mg BID	200mg BID
Arm/Group Description	100mg Fostmatinib BID	200mg Fostmatinib BID
Measure Participants	21	47
Number (95% Confidence Interval) [Patients]	2	0

Adverse Events

Arm/Group Title	100mg BID		200mg BID
Arm/Group Description	100mg Fostmatinib BID		200mg Fostmatinib BID
All Cause Mortality
	100mg BID		200mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	100mg BID		200mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/21 (14.3%)		12/47 (25.5%)
Blood and lymphatic system disorders
ANAEMIA	0/21 (0%)		1/47 (2.1%)
PANCYTOPENIA	0/21 (0%)		1/47 (2.1%)
Cardiac disorders
CARDIAC ARREST	0/21 (0%)		1/47 (2.1%)
CARDIAC FAILURE CONGESTIVE	0/21 (0%)		1/47 (2.1%)
SINUS TACHYCARDIA	0/21 (0%)		1/47 (2.1%)
SUPRAVENTRICULAR TACHYCARDIA	0/21 (0%)		1/47 (2.1%)
General disorders
PYREXIA	1/21 (4.8%)		1/47 (2.1%)
FATIGUE	0/21 (0%)		1/47 (2.1%)
Infections and infestations
PNEUMONIA	0/21 (0%)		2/47 (4.3%)
CELLULITIS	0/21 (0%)		1/47 (2.1%)
CLOSTRIDIUM DIFFICILE INFECTION	0/21 (0%)		1/47 (2.1%)
NEUTROPENIC SEPSIS	1/21 (4.8%)		0/47 (0%)
Metabolism and nutrition disorders
HYPONATRAEMIA	0/21 (0%)		1/47 (2.1%)
Musculoskeletal and connective tissue disorders
BACK PAIN	1/21 (4.8%)		0/47 (0%)
Nervous system disorders
CONVULSION	0/21 (0%)		1/47 (2.1%)
SYNCOPE	0/21 (0%)		1/47 (2.1%)
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS	0/21 (0%)		1/47 (2.1%)
Other (Not Including Serious) Adverse Events
	100mg BID		200mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		44/47 (93.6%)
Blood and lymphatic system disorders
ANAEMIA	2/21 (9.5%)		12/47 (25.5%)
THROMBOCYTOPENIA	5/21 (23.8%)		7/47 (14.9%)
NEUTROPENIA	5/21 (23.8%)		5/47 (10.6%)
Gastrointestinal disorders
DIARRHOEA	3/21 (14.3%)		16/47 (34%)
CONSTIPATION	4/21 (19%)		12/47 (25.5%)
NAUSEA	4/21 (19%)		12/47 (25.5%)
VOMITING	0/21 (0%)		9/47 (19.1%)
ABDOMINAL PAIN	1/21 (4.8%)		4/47 (8.5%)
ABDOMINAL DISTENSION	2/21 (9.5%)		2/47 (4.3%)
DYSPEPSIA	0/21 (0%)		4/47 (8.5%)
General disorders
FATIGUE	4/21 (19%)		13/47 (27.7%)
PYREXIA	4/21 (19%)		10/47 (21.3%)
OEDEMA PERIPHERAL	2/21 (9.5%)		3/47 (6.4%)
ASTHENIA	0/21 (0%)		3/47 (6.4%)
Infections and infestations
PNEUMONIA	0/21 (0%)		3/47 (6.4%)
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED	4/21 (19%)		8/47 (17%)
BLOOD ALKALINE PHOSPHATASE INCREASED	5/21 (23.8%)		5/47 (10.6%)
BLOOD CREATININE INCREASED	3/21 (14.3%)		3/47 (6.4%)
ALANINE AMINOTRANSFERASE INCREASED	3/21 (14.3%)		2/47 (4.3%)
BLOOD BILIRUBIN INCREASED	3/21 (14.3%)		0/47 (0%)
BLOOD LACTATE DEHYDROGENASE INCREASED	1/21 (4.8%)		4/47 (8.5%)
WHITE BLOOD CELL COUNT DECREASED	1/21 (4.8%)		3/47 (6.4%)
BLOOD UREA INCREASED	2/21 (9.5%)		1/47 (2.1%)
NEUTROPHIL COUNT DECREASED	2/21 (9.5%)		0/47 (0%)
Metabolism and nutrition disorders
HYPONATRAEMIA	1/21 (4.8%)		5/47 (10.6%)
DECREASED APPETITE	0/21 (0%)		5/47 (10.6%)
HYPOKALAEMIA	0/21 (0%)		4/47 (8.5%)
Musculoskeletal and connective tissue disorders
BACK PAIN	4/21 (19%)		5/47 (10.6%)
ARTHRALGIA	2/21 (9.5%)		2/47 (4.3%)
MYALGIA	1/21 (4.8%)		3/47 (6.4%)
Nervous system disorders
HEADACHE	2/21 (9.5%)		5/47 (10.6%)
SYNCOPE	0/21 (0%)		3/47 (6.4%)
Psychiatric disorders
ANXIETY	2/21 (9.5%)		4/47 (8.5%)
CONFUSIONAL STATE	0/21 (0%)		3/47 (6.4%)
Renal and urinary disorders
RENAL FAILURE ACUTE	0/21 (0%)		4/47 (8.5%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	3/21 (14.3%)		4/47 (8.5%)
COUGH	4/21 (19%)		2/47 (4.3%)
Skin and subcutaneous tissue disorders
NIGHT SWEATS	0/21 (0%)		4/47 (8.5%)
Vascular disorders
HYPERTENSION	1/21 (4.8%)		9/47 (19.1%)
HYPOTENSION	2/21 (9.5%)		3/47 (6.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.