Deferasirox in Treating Patients With Very Low, Low, or Intermediate-Risk Red Blood Cell Transfusion Dependent Anemia or Myelodysplastic Syndrome

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02943668
• Collaborator: National Cancer Institute (NCI) (NIH), Novartis Pharmaceuticals (Industry)
• Enrollment: 2
• Location: 1
• Arm: 1
• Actual Duration (Months): 21.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well deferasirox works in treating patients with very low, low, or intermediate-risk anemia or myelodysplastic syndrome that depends on red blood cell transfusions. Deferasirox may treat too much iron in the blood caused by blood transfusions.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Myelodysplastic Syndrome	Drug: Deferasirox; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the activity of iron chelation therapy (ICT) with deferasirox, in patients with anemia due to myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

1. Reduction in red blood cell (RBC) transfusion requirements. II. Hematologic improvement.

2. Change in serum ferritin levels from baseline to the end of the study as measured on a monthly basis.

3. Safety and tolerability of deferasirox.

EXPLORATORY OBJECTIVES:

1. Blood and marrow samples will be taken to study erythropoiesis and the impact of iron overload on erythropoiesis.

OUTLINE: Patients receive deferasirox orally (PO) once daily (QD). Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Deferasirox in Patients With Myelodysplastic Syndromes Who Are Anemic With Iron Overload
• Actual Study Start Date: Mar 2, 2017
• Actual Primary Completion Date: Dec 17, 2018
• Actual Study Completion Date: Dec 17, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (deferasirox) Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Deferasirox; Given PO; Other Names: Exjade ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients That Achieve Erythroid Hematologic Improvement. [At 6 months]

   As defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L

Secondary Outcome Measures

1. Change in Red Blood Cell (RBC) Transfusion Requirements [Baseline up to 12 months]

   Assessed monthly for up to twelve months.

2. Change in Serum Ferritin Levels [Baseline up to 12 months]

   Assessed monthly for up to twelve months.

3. Proportion of Patients Who Achieve Granulocyte or Platelet Hematologic Improvement [At 6 months]

   As defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Capable of giving written informed consent prior to any study-specific procedures

• Diagnosis of MDS as defined by the World Health Organization (WHO) diagnostic criteria

• Have very low, low or intermediate-risk disease by the Revised International Prognostic Scoring System (IPSS-R)

• Baseline serum ferritin level >= 100 ng/mL

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Anemia defined as: hemoglobin =< 10.0 g/dL

• Bilirubin =< 1.5 times upper limit of normal (ULN)

• Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =< 3.5 times ULN

• Serum creatinine =< 1.5 x ULN

• Estimated glomerular filtration rate (GFR) > 40 mL/min

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of deferasirox

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment; effective contraception methods include:

• Placement of an intrauterine device (IUD) or intrauterine system (IUS)

• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

• Total abstinence or (when this is in line with the preferred and usual lifestyle of the subject); periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception

• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

• Male sterilization (at least 6 months prior to screening); for female subjects on the study, the vasectomized male partner should be the sole partner for that subject

• Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential; sexually active males must use a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid

• Females with childbearing potential* must have had a negative urine or serum pregnancy test =< 7 days before the first dose of deferasirox and must also not be breastfeeding

• Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

Exclusion Criteria:

• If the patient is currently receiving erythroid stimulating agents (ESA) with plans to continue during study, less than 2 months duration of ESA prior to starting study drug and no dose escalation within 2 months of start of study drug

• If the patient is being treated with granulocyte-colony stimulating factor (GCSF) and/or a TPO-mimetic (for example, eltrombopag or romiplostim) with plans to continue during the study: Less than 2 months duration of GCSF or the TPO-mimetic treatment prior to starting study drug; or GCSF and/or TPO-mimetic has been added to ESA therapy within 2 months of start of study drug

• If patient is being treated with lenalidomide with plans to continue during the study: Stable dose for less than 3 months prior to start of study drug

• If patient is being treated with hypomethylating agents (HMA) (for example, azacitidine or decitabine) with plans to continue during the study: Stable dose for less than 6 months prior to start of study drug

• Currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

• Presence of >= 10% blast by morphologic examination of bone marrow aspirate or biopsy

• Platelets =< 50,000

• Microcytosis on screening blood cell count (CBC) (mean corpuscular volume [MCV] < 81 fL)

• Active gastrointestinal (GI) ulceration or hemorrhage

• Have a serious preexisting medical condition that, in the opinion of the investigator would preclude participation in the study (for example a GI disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome) or that would result in a life expectancy of less than 1 year

• Known hypersensitivity to deferasirox

• History of non-transfusional hemosiderosis

• Prior hematopoietic stem cell transplant for the diagnosis of MDS

• A second primary malignancy that in the judgment of the principal investigator (PI) or designee may affect the interpretation of results

• Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis

• Currently using aluminum-containing antacid products

• History of clinically significant auditory or ocular toxicity with ICT

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Bart Scott, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 2, 2019

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02943668
• Other Study ID Numbers: 9422; NCI-2016-01457; 9422; P30CA015704
• First Posted: Oct 25, 2016
• Last Update Posted: Jul 1, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Preleukemia; Anemia; Myelodysplastic Syndromes; Syndrome; Deferasirox

Study Results

Participant Flow

Arm/Group Title	Treatment (Deferasirox)
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	2
COMPLETED	1
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Deferasirox)
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	2 100%
Sex: Female, Male (Count of Participants)
Female	1 50%
Male	1 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	2 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients That Achieve Erythroid Hematologic Improvement.
Description	As defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Deferasirox)
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies Of the two participants on the study, none achieved erythroid hematologic improvement as defined by the modified IWG response criteria at 6 months.
Measure Participants	2
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Change in Red Blood Cell (RBC) Transfusion Requirements
Description	Assessed monthly for up to twelve months.
Time Frame	Baseline up to 12 months

Outcome Measure Data

Analysis Population Description

Data for the 2 participants is presented as 2 different groups to show the individual RBC transfusion requirements per month, at each point in time

Arm/Group Title	Patient 1	Patient 2
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	1	1
Transfusion requirement at Baseline	4	1
Transfusion requirement at time off-treatment	2	2

3. Secondary Outcome

Title	Change in Serum Ferritin Levels
Description	Assessed monthly for up to twelve months.
Time Frame	Baseline up to 12 months

Outcome Measure Data

Analysis Population Description

Data for the 2 participants is presented as 2 different groups to show the individual serum ferritin levels at each point in time

Arm/Group Title	Patient 1	Patient 2
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	1	1
Baseline	6025	755
1 month	6637	778
2 months	6010	827
3 months	6405	583
4 months	22360	414
5 months	7252	652
6 months	5697	776
7 months	4832	880
8 months	4054	NA
9 months	3933	NA
10 months	3728	NA
11 months	NA	NA
12 months	NA	NA

4. Secondary Outcome

Title	Proportion of Patients Who Achieve Granulocyte or Platelet Hematologic Improvement
Description	As defined by the modified International Working Group (IWG) response criteria: Erythroid response (pretreatment, <11 g/dL): Hgb increase by ≥ 1.5 g/dL Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤ 0.9 g/dL pretreatment will count in the RBC transfusion response evaluation. Platelet response (pretreatment, < 100 x 10^9/L) Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L platelets Increase from < 20 x 10^9/L to > 20 x 10^9/L and by at least 100% Neutrophil response (pretreatment, < 1.0 x 10^9/L) 1) At least 100% increase and an absolute increase > 0.5 x 10^9/L
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Deferasirox)
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	2
Count of Participants [Participants]	1 50%

Adverse Events

Time Frame	Enrollment through 30 days after the last administration of the study treatment
Arm/Group Title	Treatment (Deferasirox)
Arm/Group Description	Patients receive deferasirox PO QD. Treatment continues for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Deferasirox: Given PO Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Deferasirox)
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Serious Adverse Events
	Treatment (Deferasirox)
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Gastrointestinal disorders
Constipation	1/2 (50%)
Other (Not Including Serious) Adverse Events
	Treatment (Deferasirox)
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
Blood and lymphatic system disorders
Anemia- due to acute blood loss	1/2 (50%)
Cardiac disorders
A-fib w/ rapid ventricular rate	1/2 (50%)
Gastrointestinal disorders
Hemorrhoids	1/2 (50%)
Constipation	1/2 (50%)
Infections and infestations
Clostrid Difficile	1/2 (50%)
Sinus Infection	1/2 (50%)
Urinary tract infection	1/2 (50%)
Injury, poisoning and procedural complications
Fracture- Lft. Lateral Tibia Plateau	1/2 (50%)
Fall	1/2 (50%)
Fracture- Lft. Second Metatarsal	1/2 (50%)
Fracture- Lft. Wrist	1/2 (50%)
Investigations
Weight loss	1/2 (50%)
Alanine Amniotransferase- increased	1/2 (50%)
Asparate Aminotransferase increased	1/2 (50%)
Psychiatric disorders
Insomnia	1/2 (50%)
Renal and urinary disorders
Elevated Creatine/ urine protein	1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/2 (50%)

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.