Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01159067
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 13.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Low dose deferasirox may be safe and effective in treating patients who have undergone hematopoietic stem cell transplant and have iron overload.

PURPOSE: This pilot clinical trial studies safety and tolerability of deferasirox in hematopoietic stem cell transplant recipients who have iron overload. Effect of low dose deferasirox on labile plasma iron is also examined.

Condition or Disease	Intervention/Treatment	Phase
Iron Overload; Accelerated Phase Chronic Myelogenous 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); Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Disseminated Neuroblastoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; 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; Poor Prognosis Metastatic Gestational Trophoblastic Tumor; 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 Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; 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 Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Malignant Testicular Germ Cell Tumor; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage III Small Lymphocytic Lymphoma; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; 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 Breast Cancer; Stage IV Chronic Lymphocytic Leukemia; 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 Ovarian Epithelial Cancer; Stage IV Small Lymphocytic Lymphoma	Drug: deferasirox	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine labile plasma iron (LPI) levels in iron overloaded patients after allogeneic Hematopoietic Stem Cell Transplantation (HSCT).

2. To determine safety and tolerability of low dose deferasirox in the post allogeneic HSCT setting.

SECONDARY OBJECTIVES:

1. To determine ability of deferasirox to suppress LPI in allogeneic HSCT patients with serum ferritin over 1500 ng/ml.

2. To determine prevalence of elevated LPI in allogeneic HSCT recipients with serum ferritin over 1500 ng/ml.

3. To determine ability of low dose deferasirox to lower serum ferritin during the treatment period.

4. To correlate LPI with serum ferritin in allogeneic HSCT recipients with serum ferritin over 1500 ng/ml.

OUTLINE: Patients receive deferasirox at 10 mg/kg once daily for 6 months in the absence of unacceptable toxicity. Labile plasma iron will be measured at baseline and at weeks 4, 12, and 24. Side effects of deferasirox will be recorded.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Deferasirox Treatment and Labile Plasma Iron in Iron Overloaded Patients Who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Aug 9, 2011
• Actual Study Completion Date: Aug 9, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.	Drug: deferasirox; Given orally; Other Names: Exjade ICL670

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Elevated Labile Plasma Iron (LPI) Above Threshold (0.5 Umol/L) [At baseline]

Secondary Outcome Measures

1. Number of Patients With LPI Below 0.5 Umol/L After Treatment [Assessed through 6 months from the start of treatment]

   In patients with LPI values above threshold 0.5umol/L at baseline, number of patients had LPI suppressed below this value after treatment. Measurement of LPI is done on plasma specimens.

2. Number of Patients With Serum Ferritin Level Lower Than 1500 ng/mL After Treatment [Assessed through 6 months from the start of treatment]

   Number of patients, whose Serum Ferritin levels are lower than 1500 ng/mL at two consecutive study visits. Serum Ferritin levels are measured at screening (baseline), week 4, 8, 12, 16, 20, 24 and end of study.

3. Correlation of LPI With Serum Ferritin [Assessed through 6 months from the start of treatment]

   Both LPI and Serum Ferritin levels are measured at screening (baseline), week 4, 12, 24 and end of study. The correlation between the levels of LPI and Serum Ferritin at screening, week 4, 12, 24 and end of study will be examined and plotted.

Eligibility Criteria

Criteria

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

Inclusion

• Patients must have undergone a matched related donor, matched unrelated donor or cord blood Hematopoietic Stem Cell Transplant (HSCT) over 6 months ago

• Patients currently on Desferal (desferrioxamine) therapy will require a one day wash out prior to the first dose of study drug

• Serum ferritin >= 1500 ng/mL on two occasions two weeks apart at screening; samples must be obtained in the absence of concomitant infection

• Normal C-reactive protein level at screening

• Patients must be red cell transfusion independent for 2 months prior to enrollment

• Sexually active women must use an effective method of contraception, or must have undergone clinical documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months)

• Written informed consent by the patient

Exclusion

• Chronic hepatic GVHD with serum total bilirubin over 2 mg/dL

• Known hypersensitivity to deferasirox

• Serum creatinine above the upper limit of normal

• AST or ALT > 200 U/L during screening

• Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive and ALT above the normal range)

• History of HIV positive test result (ELISA or Western blot)

• History of drug or alcohol abuse within the 12 months prior to enrollment

• ECOG Performance Status > 2

• Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation

• Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment

• Pregnancy (as documented in required screening laboratory test) or breast feeding

• Patients who received treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days or are planning to receive other investigational drugs while participating in the study

• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug

• History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010

Sponsors and Collaborators

• City of Hope Medical Center

Investigators

• Principal Investigator: Vinod Pullarkat, MD, City of Hope Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT01159067
• Other Study ID Numbers: 09187; NCI-2010-01428
• First Posted: Jul 9, 2010
• Last Update Posted: Jun 18, 2019
• Last Verified: Nov 1, 2017

• Keywords provided by City of Hope Medical Center: HSCT, iron overload, deferasirox, labile plasma iron
• Additional relevant MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Breast Neoplasms; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Preleukemia; Lymphoma, Non-Hodgkin; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Neuroblastoma; Neoplasms, Germ Cell and Embryonal; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Carcinoma, Ovarian Epithelial; Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Hairy Cell; Leukemia, Myeloid, Chronic-Phase; Testicular Neoplasms; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Trophoblastic Neoplasms; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Hypereosinophilic Syndrome; Leukemia, Neutrophilic, Chronic; Iron Overload; Syndrome; Recurrence; Deferasirox

Study Results

Participant Flow

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Elevated Labile Plasma Iron (LPI) Above Threshold (0.5 Umol/L)
Time Frame	At baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
Measure Participants	1
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Number of Patients With LPI Below 0.5 Umol/L After Treatment
Description	In patients with LPI values above threshold 0.5umol/L at baseline, number of patients had LPI suppressed below this value after treatment. Measurement of LPI is done on plasma specimens.
Time Frame	Assessed through 6 months from the start of treatment

Outcome Measure Data

Analysis Population Description

No patient had elevated LPI level above 0.5umol/L at baseline.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
Measure Participants	0

3. Secondary Outcome

Title	Number of Patients With Serum Ferritin Level Lower Than 1500 ng/mL After Treatment
Description	Number of patients, whose Serum Ferritin levels are lower than 1500 ng/mL at two consecutive study visits. Serum Ferritin levels are measured at screening (baseline), week 4, 8, 12, 16, 20, 24 and end of study.
Time Frame	Assessed through 6 months from the start of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
Measure Participants	1
Count of Participants [Participants]	1 100%

4. Secondary Outcome

Title	Correlation of LPI With Serum Ferritin
Description	Both LPI and Serum Ferritin levels are measured at screening (baseline), week 4, 12, 24 and end of study. The correlation between the levels of LPI and Serum Ferritin at screening, week 4, 12, 24 and end of study will be examined and plotted.
Time Frame	Assessed through 6 months from the start of treatment

Outcome Measure Data

Analysis Population Description

The enrolled patient's LPI level at baseline is below 0.5 umol/L and she had both LPI and Serum Ferritin levels measured at baseline only. Therefore, no sufficient data to estimate the correlation of LPI with Serum Ferritin.

Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
Measure Participants	0

Adverse Events

Time Frame	From Cycle 1 to Cycle 6
Arm/Group Title	Arm I
Arm/Group Description	Patients receive oral deferasirox once daily for up to 6 months in the absence of unacceptable toxicity.
All Cause Mortality
	Arm I
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	1/1 (100%)
Blood and lymphatic system disorders
Iron overload	1/1 (100%)	1
Neutrophils/granulocytes (ANC/AGC)	1/1 (100%)	2
Platelets	1/1 (100%)	10
Cardiac disorders
Hypotension	1/1 (100%)	1
Gastrointestinal disorders
Anorexia	1/1 (100%)	1
Nausea	1/1 (100%)	6
Vomiting	1/1 (100%)	1
Hemorrhage, GU	1/1 (100%)	5
General disorders
Fatigue (asthenia, lethargy, malaise)	1/1 (100%)	1
Fever	1/1 (100%)	1
Rigors/chills	1/1 (100%)	1
Pain	1/1 (100%)	5
Infections and infestations
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)	1/1 (100%)	2
Infection with normal ANC or Grade 1 or 2 neutrophils	1/1 (100%)	1
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)	1/1 (100%)	6
AST, SGOT(serum glutamic oxaloacetic transaminase)	1/1 (100%)	7
Albumin, serum-low (hypoalbuminemia)	1/1 (100%)	1
Alkaline phosphatase	1/1 (100%)	6
Creatinine	1/1 (100%)	4
Glucose, serum-high (hyperglycemia)	1/1 (100%)	1
Magnesium, serum-high (hypermagnesemia)	1/1 (100%)	3
Proteinuria	1/1 (100%)	2
Sodium, serum-low (hyponatremia)	1/1 (100%)	2
Uric acid, serum-high (hyperuricemia)	1/1 (100%)	3
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy)	1/1 (100%)	1
Nervous system disorders
Mood alteration	1/1 (100%)	1
Neuropathy: sensory	1/1 (100%)	1
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory	1/1 (100%)	1
Cough	1/1 (100%)	2
Dyspnea (shortness of breath)	1/1 (100%)	1
Nasal cavity/paranasal sinus reactions	1/1 (100%)	1
Skin and subcutaneous tissue disorders
Hypopigmentation	1/1 (100%)	6
Ulceration	1/1 (100%)	1

Limitations/Caveats

[Not Specified]

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.