Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 2 Study of Therapeutic Effect and Safety of Combined Hydroxyurea With Recombinant Human Erythropoietin.
Brief Summary: The study hypothesis that treatment with Erythropoietin (EPO) combined with Human Erythropoietin (HUO) therapy will result in hematologic improvement in thalassemia intermedia patients.

Second is to determine whether any of the following correlate with improved hematologic response:

A decrease in hemolysis, as assayed by a decrease in LDH, compared to baseline levels,baseline Erythropoietin levels,baseline hemoglobin levels and baseline reticulocyte counts (or % circulating nucleated erythroblasts/100 WBCs).

Goal:

The aim is to assess the possibility of steady increase of hemoglobin levels in thalassemia intermedia patients by at least 1g/dl above baseline levels during therapy using Hydroxyurea and Erythropoietin, growth evaluation,quality of life (QoL) and decline transfusion requirements during study period. Also to report and compare adverse events with other published data regarding.


Options:
A: Inclusion Criteria:

* Patients meeting all of the following criteria will be considered for admission to the trial:

  * Diagnosis of NTDT;
  * Ages 18-65 years;
  * ECOG: 0\~2 scores;
  * If not blood transfusion,the level of HB\<90g/dl, or blood transfusion to maintain the HB;
  * Sign an informed consent agreeing to the clinical trial participation.

Exclusion Criteria:

* Patients presenting with any of the following criteria will not be included in the trial:

  * Patients received hydroxycarbamide, Yisui Shengxue Granule in three months;
  * Women during Pregnancy, breastfeeding or those of childbearing age who do not want to take contraceptive measures;
  * Patients had comorbidities like severe heart or lung diseases, liver dysfunction, cerebrovascular, cardiovascular, liver, kidney, tumor or other serious primary diseases;
  * Patients Allergic to the drug ingredients;
  * Patients with any Mental problem;
  * Patients had Participated in other drug clinical trials in the past 1 month;
  * Patients had a history of venous or arterial thrombosis;
  * In certain circumstances that the researchers determined it was not suitable for the research.
B: Inclusion Criteria:

* Males and females between 12 and 60 years of age
* Diagnosis of SCD, type Hb SS or Hb S-B0 Thalassemia
* At least 1 episode of SCD pain crisis, acute chest syndrome, other acute SCD complications, or leg ulcers in the 12 months prior to screening
* Not being treated with Hydroxyurea (HU); if HU treatment has been previously administered and then discontinued, at least 3 months must have elapsed since last dose of HU
* If subject has been transfused in the 3 months prior to screening, then Hb A level \< 20% at screening
* Baseline Hb F level obtained within 14 days prior to randomization
* Able to swallow tablets
* Able and willing to give informed consent and/or assent
* If subject is a woman of child-bearing potential (WCBP), she must have a negative serum pregnancy test within 14 days of first dose of HQK-1001 and a negative urine pregnancy test prior to dosing on Day 1
* If a subject is a WCBP, she must agree to use an effective form of contraception starting at screening and for one month after HQK-1001 discontinuation
* Sexually active male subjects who have not had a vasectomy must agree to use latex condoms with WCBP partners or ensure that their partner(s) use an effective form of contraception starting at screening and for one month after HQK-1001 discontinuation.

Exclusion Criteria:

* Assigned to a regular transfusion program
* Use of erythropoiesis stimulating agents within 90 days prior to screening
* An SCD pain crisis or SCD-related acute complication within 3 weeks prior to randomization
* More than 5 SCD pain crisis or SCD-related acute complications within 12 months prior to screening
* Pulmonary hypertension requiring therapy
* ALT or AST \> 3x ULN
* Serum creatinine \> 1.5x ULN
* Serum amylase levels \> 1.5x ULN
* Serum lipase level \> 1.5x ULN
* A serious, concurrent illness that would limit ability to complete or comply with the study requirements
* An acute illness (e.g., febrile, GI, respiratory) within 72 hours prior to screening
* History of syncope, clinically significant dysrhythmias or resuscitation from sudden death due to SCD-related complication
* Symptomatic peptic ulcer, hiatus hernia, or gastroesophageal reflux disease (GERD)
* History of pancreatitis
* Chronic opiate use, which, in the view of the investigator, could confound evaluation of an investigational drug
* Current abuse of alcohol or drugs
* Use of another investigational agent within 4 weeks or 5 half-lives, whichever is longer, prior to screening
* Currently pregnant or breast feeding a child
* Known infection with HIV-1
* Infection with hepatitis B or hepatitis C, such that subjects are currently on anti-viral therapy or will be placed on therapy
C: Inclusion Criteria:

* Beta-thalassemia and beta thalassemia-hemoglobin E (HbE), as confirmed by DNA testing
* Transfusion independent for at least 120 days before study entry
* Red blood cell folate levels above the lower limit of normal

Exclusion Criteria:

* Absolute neutrophil count (ANC) less than 2000/mm3 in the 8 weeks before study entry or a history of chronic neutropenia, defined as an ANC less than 2000/mm3
* Platelet count less than 100,000/mm3 or greater than 1,000,000/mm3 in the 8 weeks before study entry
* Family history of an inherited disease resulting in low ANC or bone marrow failure
* Serum creatinine level greater than 2 mg/dL in the 8 weeks before study entry
* Evidence of liver disease, as defined by one or more of the following conditions:

  1. Alanine aminotransferase (ALT) level greater than 3 times the upper limit of normal in the 8 weeks before study entry
  2. Serum albumin level less than 3 g/dL in the 8 weeks before study entry
  3. Evidence of cirrhosis on liver biopsy obtained in the 6 months before study entry
* Approaching death; has concurrent liver, kidney, cardiac, or metabolic disease; or has any disease of such severity that death within 7 to 10 days of study entry is likely
* Pregnant, planning to become pregnant, or breastfeeding
* Sexually active female of childbearing potential who is unwilling to use at least two acceptable methods of contraception, as determined by the investigator
* Sexually active male whose partner is of child-bearing potential and who is unwilling to use at least two acceptable methods of contraception, as determined by the investigator, during and for 2 months after decitabine treatment
* Diagnosed with cancer (except non-melanoma skin cancer) in the 5 years before study entry. In particular, suspicion or evidence of myelodysplastic syndrome (MDS) on clinically indicated bone marrow aspirate or a family history of MDS or concurrent leukemia
* HIV infection
* Not expected to be able to complete 24 weeks of study follow-up
* Currently being treated with any experimental or fetal hemoglobin modulating agent
* Current participation in any other studies of investigational drugs or devices
* Unable to comply with study medication regimen
* Any condition, which in the opinion of the investigator, would place the individual at undue risk if treated with twice-weekly low-dose decitabine for 12 weeks
D: Inclusion Criteria:

* Patients with thalassemia intermedia. Diagnosis based on genetic mutations, hemoglobin electrophoresis and characteristic clinical data at presentation.
* Require different transfusion requirements and not transfusion dependent.
* Have a baseline hemoglobin of less than or equal to 6-8g/dl.
* Patients with normal renal and liver function.

Exclusion Criteria:

* Evidence of active hepatitis (ALT \> 5 times above ULN).
* Evidence of renal impairment (serum creatinine \> ULN).
* Patients who are dependent on red blood cell transfusions.

Answer: D