Imatinib Mesylate in Treating Patients With Myelofibrosis

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00245128
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 10
• Location: 1
• Duration (Months): 74
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects of imatinib mesylate and how well it works in treating patients with myelofibrosis.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders	Drug: imatinib mesylate	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the safety, efficacy, and tolerability of imatinib mesylate in patients with myelofibrosis with myeloid metaplasia.

• Determine the 3-, 6-, and 12-month major and minor erythroid response rates in patients treated with this drug.

Secondary

• Determine reduction in marrow fibrosis in patients treated with this drug.

• Determine decrease in spleen size in patients treated with this drug.

OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.

Patients receive oral imatinib mesylate once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients who do not experience a minor erythroid response or a 50% reduction in spleen size after 6 months of treatment are removed from the study. Patients experiencing clinical benefit (e.g., ongoing erythroid response) after 1 year of treatment may continue treatment with imatinib mesylate as above at the discretion of the principal investigator.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Pilot Study to Determine the Safety and Preliminary Efficacy of Imatinib Mesylate (Gleevec) in Patients With Myelofibrosis With Myeloid Metaplasia
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Mar 1, 2007
• Actual Study Completion Date: Oct 1, 2011

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Major and/or Minor Erythroid Responses at 3, 6, and 12 Months of Therapy [At 3,6, and 12 months of therapy]

   A major response = transfusion independent or a>2.0g/dl rise in hemoglobin without transfusion maintained for at least 8 weeks. Minor response= > 1 to 2.0g/dl incremental rise in hemoglobin maintained for at lease 8 weeks with a decrease in transfusion requirements of at least 50% compared to the mean transfusion requirement during the 8 week pre-study period.

Secondary Outcome Measures

1. Reduction in Marrow Fibrosis and Decrease in Spleen Size [After 6 and 12 months of therapy]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Diagnosis of myelofibrosis with myeloid metaplasia (MMM), defined by all of the following:

• Leukoerythroblastic blood picture

• Fibrosis involving > 1/3 sectional area of bone marrow biopsy

• Splenomegaly (unless patient has undergone prior splenectomy)

• Philadelphia chromosome negative

• No myelodysplastic syndrome

• No systemic disorders associated with marrow fibrosis

• Red blood cell transfusion dependent, defined by 1 of the following:

• Patient has required ≥ 2 units of red blood cells every 4 weeks within the past 8 weeks

• Hemoglobin ≤ 8 g/dL on ≥ 3 occasions (≥ 2 weeks apart ) over the past 8 weeks

• No evidence of disease transformation to acute myelogenous leukemia, defined as > 20% blasts in bone marrow and/or peripheral blood

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3

• Platelet count > 50,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• AST or ALT ≤ 2 times ULN (unless due to extramedullary hematopoiesis in the liver)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No New York Heart Association grade III-IV heart disease

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment

• No serious, uncontrolled medical condition

• No patients who are considered potentially unreliable or with a history of noncompliance to medical regimens

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 2 weeks since prior interferon alfa

Chemotherapy

• No concurrent chemotherapy except hydroxyurea to control elevated blood counts

Endocrine therapy

• More than 4 weeks since prior corticosteroids, danazol, or other androgens for MMM

Other

• More than 4 weeks since other prior treatment for MMM

• No other concurrent experimental drug therapy for MMM

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239-3098

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Mauro, MD, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00245128
• Other Study ID Numbers: CDR0000445435; OHSU-541; OHSU-HEM-01071-L
• First Posted: Oct 27, 2005
• Last Update Posted: Jan 13, 2012
• Last Verified: Dec 1, 2011

• Keywords provided by OHSU Knight Cancer Institute: chronic idiopathic myelofibrosis; polycythemia vera; essential thrombocythemia
• Additional relevant MeSH terms: Primary Myelofibrosis; Myeloproliferative Disorders; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Once daily oral administration of Imatinib Mesylate at a dose of 600mg for 12 months.
Period Title: Overall Study
STARTED	10
COMPLETED	0
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Once daily oral administration of Imatinib Mesylate at a dose of 600mg for 12 months.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 30%
>=65 years	7 70%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (11.00303)
Sex: Female, Male (Count of Participants)
Female	1 10%
Male	9 90%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Major and/or Minor Erythroid Responses at 3, 6, and 12 Months of Therapy
Description	A major response = transfusion independent or a>2.0g/dl rise in hemoglobin without transfusion maintained for at least 8 weeks. Minor response= > 1 to 2.0g/dl incremental rise in hemoglobin maintained for at lease 8 weeks with a decrease in transfusion requirements of at least 50% compared to the mean transfusion requirement during the 8 week pre-study period.
Time Frame	At 3,6, and 12 months of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Once daily oral administration of Imatinib Mesylate at a dose of 600mg for 12 months.
Measure Participants	0

2. Secondary Outcome

Title	Reduction in Marrow Fibrosis and Decrease in Spleen Size
Time Frame	After 6 and 12 months of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Imatinib Mesylate (Gleevec)
Arm/Group Description	Once daily oral administration of Imatinib Mesylate at a dose of 600mg for 12 months.
All Cause Mortality
	Imatinib Mesylate (Gleevec)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Imatinib Mesylate (Gleevec)
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Sepsis	1/10 (10%)
Elevated CPK	1/10 (10%)
Acute leukemia	1/10 (10%)
Febrile neutropenia	2/10 (20%)
Hypocalcemia	1/10 (10%)
Hodgkin's Disease	1/10 (10%)
Thrombocytopenia	1/10 (10%)
Eye disorders
Optic nerve atrophy	1/10 (10%)
Retinal detachment	1/10 (10%)
Ptosis	1/10 (10%)
Gastrointestinal disorders
Lower abdominal pain	1/10 (10%)
Fatal diverticulitis, gastrointestinal peforation, peritonitis	1/10 (10%)
Fatal pancreatitis	1/10 (10%)
General disorders
Fever	2/10 (20%)
Death	1/10 (10%)
Infections and infestations
Bacterial meningitis	1/10 (10%)
Musculoskeletal and connective tissue disorders
Myositis	1/10 (10%)
hospitalization for bone pain	1/10 (10%)
Rhabdomyolysis	1/10 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liver abscess	1/10 (10%)
Nervous system disorders
Parkinson's Disease	1/10 (10%)
Extra pyramidal symptoms	1/10 (10%)
Brain herniation	1/10 (10%)
Bell's Palsy	1/10 (10%)
Plaques of demyelination	1/10 (10%)
Renal and urinary disorders
Oncocytoma	1/10 (10%)
Ureteric Calculus	1/10 (10%)
Bilirubin and lipase	1/10 (10%)
Cholelithiasis	1/10 (10%)
Hydronephrosis	1/10 (10%)
Urothelial Carcinoma	1/10 (10%)
Interstitial nephritis	1/10 (10%)
Hemorrhagic cystitis	1/10 (10%)
Reproductive system and breast disorders
Spontaneous Abortion	2/10 (20%)
Menorrhagia	1/10 (10%)
Prostate Cancer	1/10 (10%)
Priapism	1/10 (10%)
Squamous cell carcinoma of the penis	1/10 (10%)
Leydig cell hyperplasia	1/10 (10%)
Metastases of breast cancer	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusions	1/10 (10%)
Hypersensitivity Pneumonitis	1/10 (10%)
Oesophageal adenocarcinoma	1/10 (10%)
Haemothorax	1/10 (10%)
Esophageal fistula	1/10 (10%)
Chronic obstructive airways disease	1/10 (10%)
Vascular disorders
ateriovenus malformation	1/10 (10%)
Other (Not Including Serious) Adverse Events
	Imatinib Mesylate (Gleevec)
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Blood and lymphatic system disorders
Hypoglycemia	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Rash	1/10 (10%)	1

Limitations/Caveats

Early termination/results were never analyzed due to negative study results from other similar studies.

More Information

Certain Agreements

All Principal Investigators ARE 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.