Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

Study Overview
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Brief Summary
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RATIONALE: Deferasirox may remove excess iron from the body caused by blood transfusions. PURPOSE: This clinical trial studies deferasirox in treating iron overload caused by blood transfusions in patients with hematologic malignancies.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the effects of the iron-chelating agent deferasirox on changes in: neutrophil function; macrophage function; lymphocyte function. SECONDARY OBJECTIVES: I. To determine the effect of chelation on the incidence of bacterial, viral and fungal infections documented by clinical, microbiologically-proven versus radiologically-proven criteria. II. To determine the effect of iron chelation on mortality and morbidity with incidence of the following parameters: Need for hospitalization; Duration of hospitalization; Need for ventilatory support; Need for exchange transfusion/apheresis; Need for treatment with antifungals or antibiotics for documented infections. OUTLINE: Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity.

Official Title
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Impact of Intervention With Deferasirox on the Immune Function of Patients With Hematologic Diseases and Transfusion-Related Iron Overload

Conditions
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Stage II Cutaneous T-cell Non-Hodgkin Lymphoma, Acute Undifferentiated Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Grade III Lymphomatoid Granulomatosis, Adult Langerhans Cell Histiocytosis, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Contiguous Stage II Adult Burkitt Lymphoma, Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Contiguous Stage II Adult Lymphoblastic Lymphoma, Contiguous Stage II Grade 1 Follicular Lymphoma, Contiguous Stage II Grade 2 Follicular Lymphoma, Contiguous Stage II Grade 3 Follicular Lymphoma, Contiguous Stage II Mantle Cell Lymphoma, Contiguous Stage II Marginal Zone Lymphoma, Contiguous Stage II Small Lymphocytic Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, de Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Mast Cell Leukemia, Myelodysplastic Syndrome With Isolated Del(5q), Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Myeloid/NK-cell Acute Leukemia, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Burkitt Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Previously Treated Myelodysplastic Syndromes, Primary Myelofibrosis, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Anemia, Refractory Multiple Myeloma, Secondary Acute Myeloid Leukemia, Secondary Myelofibrosis, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage I Adult Burkitt Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Mixed Cell Lymphoma, Stage I Adult Diffuse Small Cleaved Cell Lymphoma, Stage I Adult Hodgkin Lymphoma, Stage I Adult Immunoblastic Large Cell Lymphoma, Stage I Adult Lymphoblastic Lymphoma, Stage I Adult T-cell Leukemia/Lymphoma, Stage I Cutaneous T-cell Non-Hodgkin Lymphoma, Stage I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Mantle Cell Lymphoma, Stage I Marginal Zone Lymphoma, Stage I Multiple Myeloma, Stage I Mycosis Fungoides/Sezary Syndrome, Stage I Small Lymphocytic Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage II Adult T-cell Leukemia/Lymphoma, Stage II Multiple Myeloma, Stage II Mycosis Fungoides/Sezary Syndrome, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Testicular Lymphoma, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Adult Acute Myeloid Leukemia, Waldenstrom Macroglobulinemia

Intervention / Treatment
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* Drug: deferasirox
* Other: laboratory biomarker analysis
* Other: enzyme-linked immunosorbent assay


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a pathology confirmed diagnosis of one of the following: myelodysplastic syndrome (MDS); acute leukemia; multiple myeloma; myelofibrosis; lymphoma; chronic anemia; sickle cell anemia Iron score >= 2 Absolute Neutrophil Count (ANC) >= 1,000 Platelets >= 50,000 Albumin >= 2 g/dL Alkaline phosphatase =< 5X Upper Limit of Normal (ULN) Total bilirubin =< 1.5 Creatinine =< 2X age-appropriate Upper Limit of Normal (ULN) OR creatinine clearance >= 40 ml/min Serum Glutamic Oxaloacetic Transaminase (SGOT) [AST] and Serum Glutamic Pyruvic Transaminase (SGPT) [ALT] =< 5X Upper Limit of Normal (ULN) Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Patients with active disease undergoing chemotherapy treatment Patient who have been treated with rituximab or immunomodulating drugs =< 1 month prior to enrollment HIV-positive patients Hepatitis-C positive patients Women who are pregnant or breastfeeding Patients on hemodialysis/patients with renal failure Patients with sepsis or acute illness Known hypersensitivity to deferasirox Patients with moderate or severe hearing loss as defined by audiogram

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral deferasirox once daily for up to 6 months or until blood counts recover in the absence of disease progression or unacceptable toxicity. | Drug: deferasirox<br>* Given orally<br>* Other names: ICL670;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: enzyme-linked immunosorbent assay<br>* Correlative studies<br>* Other names: ELISA;|
| No Intervention: control arm<br>blood tested on healthy patients | |
| No Intervention: correlative<br>treated off study with or without oral deferasirox (patient choice) but lab draws to gather lab analysis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Mean Neutrophil Values (as Measured by Lab) for Arm 1 (Other Arms Were Used for Calibration Only) | Changes in Neutrophils between baseline and mean neutrophils values during treatment (measured after each dose) | Baseline, up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for Hospitalization, Ventilator Support, Exchange Transfusion/Apheresis or Treatment With Antifungals or Antibiotics | Records will be assessed at baseline and prospectively while on study. | Baseline, up to 6 months | 
| Cumulative Incidence of Documented Bacterial, Fungal, and Viral Infections | Records will be assessed at baseline and prospectively while on study. | Baseline, up to 6 months |