WO2013019220A1 - Compositions et procédés de traitement du syndrome myélodysplasique - Google Patents

Compositions et procédés de traitement du syndrome myélodysplasique Download PDF

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Publication number
WO2013019220A1
WO2013019220A1 PCT/US2011/046316 US2011046316W WO2013019220A1 WO 2013019220 A1 WO2013019220 A1 WO 2013019220A1 US 2011046316 W US2011046316 W US 2011046316W WO 2013019220 A1 WO2013019220 A1 WO 2013019220A1
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WIPO (PCT)
Prior art keywords
ezatiostat
salt
administered
administration
lenalidomide
Prior art date
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PCT/US2011/046316
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English (en)
Inventor
Gail L. Brown
Lixin Meng
Original Assignee
Telik, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
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Priority to PCT/US2011/046316 priority Critical patent/WO2013019220A1/fr
Publication of WO2013019220A1 publication Critical patent/WO2013019220A1/fr
Priority to IL230690A priority patent/IL230690A0/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration

Definitions

  • This invention relates to compositions and methods for treating myelodysplasia syndrome.
  • MDS Myelodysplasia syndrome(s) refers to a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis (blood cell production) involving one or more cell lineages (red blood cells, white blood cells or platelets) and a variable risk of transformation to acute myeloid leukemia (AML). This syndrome becomes more common with age. It is estimated that MDS affects
  • Ezatiostat and its salts are disclosed in US Patent No. 5,763,570.
  • Ezatiostat has the IUPAC chemical name of ethyl (2S)-2-amino-5-[[(2R)-3-benzylsulfanyl-l-[[(7R)-2- ethoxy-2-oxo- 1 -phenylethyl] amino] - 1 -oxopropan-2-yl] amino] -5-oxopentanoate.
  • ezatiostat hydrochloride (USAN)
  • U.S. Patent Application No. 13/041,136 filed March 4, 2011, describes ansolvate and polymorphs of ezatiostat hydrochloride.
  • Ezatiostat hydrochloride has been evaluated for the treatment of MDS, in a Phase I-IIa study using a liposomal formulation (US Patent No.
  • This invention relates to the discovery of the problem that patients with a myelodysplasia syndrome who have been treated with a DNA methyltransferase inhibitor did not respond to treatment with ezatiostat hydrochloride.
  • This invention is further based on the surprising discovery that the response rate to ezatiostat hydrochloride is increased in patients who had lenalidomide treatment prior to administration of ezatiostat hydrochloride.
  • this invention is directed to a method for treating a myelodysplasia syndrome in a patient who has been treated with a DNA
  • methyltransferase inhibitor which method comprises administering to said patient lenalidomide prior to and/or concurrently with administration of ezatiostat or a salt thereof.
  • ezatiostat or a salt thereof is administered by a dosing regimen described in U.S. Patent Application No. 13/108,752, titled “COMPOSITIONS AND METHODS FOR TREATING MYELODYSPLASTIC SYNDROME,” filed May 16, 2011, which is incorporated by reference in its entirety and claims priority to US Provisional Application No. 61/352,371, filed on June 7, 2010.
  • ezatiostat or a salt thereof may be administered in cycles of 2 gram/day orally for 3 weeks on/1 week off, or cycles of 3 gram/day orally for 2 weeks on/1 week off.
  • Equivalent ezatiostat doses for ezatiostat itself or other ezatiostat salts, or for other routes of administration may also be used.
  • ezatiostat or a salt thereof can be administered as a tablet formulation.
  • a tablet formulation is disclosed in U.S. Patent Application No.
  • this invention provides a composition for treating a
  • methyltransferase inhibitor which composition comprises lenalidomide, ezatiostat or a salt thereof, and optionally a pharmaceutically acceptable excipient.
  • this invention provides a kit of parts for treating a myelodysplasia syndrome in a patient who has been treated with a DNA
  • this invention provides use of ezatiostat or a salt thereof for the preparation of a medicament for treating a myelodysplasia syndrome in a patient who has been treated with a DNA methyltransferase inhibitor, wherein lenalidomide is administered to said patient prior to and/or concurrently with administration of the ezatiostat or a salt thereof.
  • compositions and methods include the recited elements, but do not exclude others.
  • Consisting essentially of when used to define compositions and methods shall mean excluding other elements of any essential significance to the combination for the stated purpose. Thus, a composition consisting essentially of the elements as defined herein would not exclude other materials or steps that do not materially affect the basic and novel characteristic(s) of the claimed invention.
  • Consisting of means excluding more than trace elements of other ingredients and substantial method steps. Embodiments defined by each of these transition terms are within the scope of this invention.
  • Lenalidomide is an immunomodulatory agent with antiangio genie and antineoplastic properties. It has the chemical name of 3-(4-amino-l-oxoisoindolin-2-yl)piperidine-2,6-dione or l-oxo-2-(2,6- dioxopiperidin-3-yl)-4-aminoisoindoline or 3-(7-amino-3-oxo-lH-isoindol-2- yl)piperidine-2,6-dione, and CAS registry number of 191732-72-6. Lenalidomide is indicated for the treatment of patients with transfusion-dependent due to low- or intermediate- 1 risk MDS associated with a deletion 5q cytogenetic abnormality.
  • Lenalidomide is available in 5 milligram (mg), 10 mg, 15 mg and 25 mg capsules for oral administration.
  • the term "therapeutically effective amount” refers to the amount of either lenalidomide or ezatiostat or a salt thereof that is an amount sufficient to effect treatment, as defined herein, when administered to a subject in need of such treatment.
  • the therapeutically effective amount will be up to 3.5 grams (g) of ezatiostat or a salt thereof administered per day.
  • ezatiostat or a salt thereof is administered in an amount of 2 grams per day and, more preferably, is administered twice a day in equal 1 gram doses.
  • Such a therapeutically effective amount is particularly relevant when the treatment regimen is for 3 weeks of administration of ezatiostat or a salt thereof followed by a week of no administration of the drug.
  • the therapeutically effective amount will be up to 3 grams of ezatiostat or a salt thereof administered in a single dose, or in 2 equal daily doses of up to 1.5 grams.
  • Such a therapeutically effective amount is particularly relevant when the treatment regimen is for 2 weeks of administration of ezatiostat or a salt thereof followed by a week of no administration of the drug.
  • the dosing regimen employs 2 grams of ezatiostat or a salt thereof administered in an amount of 1 gram doses twice a day either under continuous administration or with administration for 3 weeks followed by a week of no administration of the drug.
  • the therapeutically effective amount will provide efficacious results in at least about 10 % of the treated population, and preferably at least about 15 %.
  • treatment means any treatment of MDS in a patient which produces one or more of the following:
  • the term "patient” refers to mammals and includes humans and non-human mammals.
  • this invention is directed to a method for treating a
  • DMTIs also known as demethylating agents, are a class of agents that inhibit methylation of DNA through inhibition of the DNA methyltransferase activity.
  • Methylation of DNA is a major mechanism that regulates gene expression in cells. When there is an increase in DNA methylation this can result in the blockage of the activity of "suppressor genes" that regulate cell division and growth.
  • Examples of DMTIs include analogs of the nucleoside deoxycitidine, such as azacitidine (5-azacytidine), decitabine (5-aza-2'-deoxycytidine), l-P-d-arabinofuranosyl-5- azacytosine and dihydro-5-azacytidine; and antisense oligodeoxynucleotide, such as MG98 (by MGI Pharma, Inc.), which is directed against the 3 '-untranslated region of the DNA methyltransferase-1 enzyme mRNA and is now under clinical study.
  • MG98 by MGI Pharma, Inc.
  • Other DMTIs are described in Lyko F and Brown R., J. Natl. Cancer Inst, 2005; 97(20): 1498-506, which is incorporated hereby by reference in its entirety.
  • 5-Azacytidine (or azacitidine (INN), Vidaza®, CAS registry number 320-67-2), is an analogue of cytidine and has the formula:
  • Zebularine (CAS registry number of 3690-10-6) is another DMTI, which has the formula:
  • DMTIs cause many side effects, including, but are not limited to: low blood counts (where white, red blood cells and platelets may temporarily decrease, which may put the patient at increased risk for infection, anemia and/or bleeding, and may increase the need for blood or platelet transfusions), fatigue, fever, nausea, cough, petechiae (which can occur with low platelet count), constipation, diarrhea, hyperglycemia, headache, difficulty sleeping, swelling, low albumin, low magnesium, chills, low potassium, bruising, rash, low sodium, dizziness, generalized aches and pains, cardiac murmur, poor appetite, sore throat, abdominal pain, high bilirubin blood level, high potassium, mouth sores, drowsiness, abnormal liver function blood tests, confusion, anxiety, itching, and heartburn.
  • low blood counts where white, red blood cells and platelets may temporarily decrease, which may put the patient at increased risk for infection, anemia and/or bleeding, and may increase the need for blood or platelet transfusions
  • fatigue fever
  • this invention is directed to a method for treating a myelodysplasia syndrome in a patient in need thereof who has been treated with a DNA methyltransferase inhibitor, which method comprises administering to said patient an amount of lenalidomide prior to and/or currently with administration of a therapeutically effective amount of ezatiostat or a pharmaceutically acceptable salt thereof.
  • the patient has been treated with at least one dosage of a DMTI. In some embodiments, the patient has been treated with the DMTI for at least 2 days, 3 days, 4 days, 5 days, or 6 days. In some embodiments, the patient has been treated with the DMTI for at least one week, two weeks or three weeks. In some embodiments, the patient has completed at least 1, 2, 3, 4, 5, or 6 treatment cycles. In some
  • the DMTI treatment is immediately prior to the administration of ezatiostat or a salt thereof.
  • immediate means that the last DMTI dosage is administered no more than about one day prior to the first administration of ezatiostat or a salt thereof.
  • the DMTI treatment is less than 1 week prior to the administration of ezatiostat or a salt thereof.
  • the DMTI treatment is less than 1 month prior to the administration of ezatiostat or a salt thereof.
  • the DMTI treatment is less than 2 months, 6 months, or 12 months prior to the administration of ezatiostat or a salt thereof.
  • the patient needs concurrent treatment with DMTI and ezatiostat or a salt thereof.
  • lenalidomide is administered prior to administration of ezatiostat or a salt thereof.
  • a typical lenalidomide treatment schedule involves a 28-day- cycle, during which lenalidomide is administered once a day every day for 21 days (3 weeks) followed by an interruption of 7 days (1 week) when no lenalidomide is administered. This 28-day-cycle can be repeated for a duration of up to 6 months.
  • Lenalidomide capsules have four different strengths: 5 mg, 10 mg, 15 mg, and 25 mg.
  • the patient is treated with at least one dosage of lenalidomide prior to administration of ezatiostat or a salt thereof.
  • the patient is treated with lenalidomide for at least 2 days, 3 days, 4 days, 5 days, or 6 days prior to administration of ezatiostat or a salt thereof.
  • the patient is treated with lenalidomide for at least one week, two weeks or three weeks prior to administration of ezatiostat or a salt thereof.
  • the patient is treated with lenalidomide for 1, 2, 3, 4, 5, or 6 treatment cycles prior to administration of ezatiostat or a salt thereof.
  • the patient is treated with the entire 6- month lenalidomide treatment regimen prior to administration of ezatiostat or a salt thereof.
  • the patient is concurrently administered lenalidomide and ezatiostat or a salt thereof.
  • the patient may or may not be treated with lenalidomide prior to administration of ezatiostat or a salt thereof.
  • the lenalidomide treatment may continue with administration of ezatiostat or a salt thereof at the same dosage and/or frequency, or at a reduced dosage and/or frequency, or treatment with lenalidomide may completely stop.
  • lenalidomide and ezatiostat or a salt thereof can be administered in any manner in which the pharmacological effects of both are manifested in the patient at the same time.
  • concurrent administration of lenalidomide and ezatiostat or a salt thereof can be administered in any manner in which the pharmacological effects of both are manifested in the patient at the same time.
  • lenalidomide and ezatiostat or a salt thereof does not require that a single pharmaceutical composition, the same dosage form, or the same route of administration be used for the two agents.
  • the two agents do not need to be administered at the same time or for a similar length of time.
  • a concurrent administration may be the administration of a first and second pharmaceutical composition comprising lenalidomide and ezatiostat or a salt thereof, respectively.
  • the term "concurrent" includes both simultaneous delivery as well as sequential delivery wherein each drug is administered separately in a manner that provides serum levels of both drugs in the patient at the same time.
  • lenalidomide when administered concurrently with ezatiostat or a salt thereof, lenalidomide is administered in the typical 28-day-cycle as described above and may be given in any of the dosage strengths. In some embodiments, lenalidomide is administered at a reduced dosage and frequency, for example, lenalidomide may be administered once every other day, once every 3, 4, 5, or 6 days. Or it may be administered once a week or may be discontinued while treatment with ezatiostat or a salt thereof continues.
  • the patient's prior exposure to DMTI is before
  • the patient's prior exposure to DMTI is after administration of lenalidomide to the patient. In some embodiments, the patient's prior exposure to DMTI is concurrent with administration of lenalidomide to the patient.
  • ezatiostat or a salt thereof for example, ezatiostat hydrochloride
  • ezatiostat hydrochloride is administered by a dosing regimen described in U.S. Patent Application No. 13/108,752, titled "COMPOSITIONS AND METHODS FOR
  • ezatiostat or a salt thereof is administered in a therapeutically effective amount.
  • ezatiostat or a salt thereof is
  • ezatiostat or a salt thereof is administered daily for at least 2 weeks. In some embodiments, ezatiostat or a salt thereof is administered daily for at least 3 weeks.
  • ezatiostat or a salt thereof is administered in 1 gram dosages twice a day for three weeks followed by an interruption of one week where ezatiostat or a salt thereof is not administered. After the interruption, the regimen can be repeated as necessary. This regimen may be referred to as the "three-week regimen.”
  • ezatiostat or a salt thereof is
  • the patient is treated continuously with a therapeutically effective amount of ezatiostat or a salt thereof of up to 3 grams per day preferably administered in up to 1.5 gram dosages twice a day.
  • ezatiostat or a salt thereof can be administered so long as the patient is in need of and can tolerate such treatment. It is contemplated that in this embodiment, the therapeutically effective amount of ezatiostat or a salt thereof may be less or more than that when there is an interruption in the treatment regimen. This regimen may be referred to as the
  • the treatment with ezatiostat or a salt thereof may involve one or a combination of two or more of the dosing regimens described herein.
  • the following are exemplifying dosing schedules of ezatiostat hydrochloride:
  • ezatiostat or another salt thereof may replace ezatiostat hydrochloride in the above dosings.
  • the interval between the first and second doses be from about 6 to 14 hours and preferably between about 8 and 14 hours.
  • ezatiostat or a salt thereof can be administered intravenously as a lipid formulation such as those described in U.S. Patent No. 7,029,695 which is incorporated by reference in its entirety.
  • ezatiostat or a salt thereof can be administered orally. In another embodiment, ezatiostat or a salt thereof can be administered as a tablet
  • this invention provides a composition for treating a
  • methyltransferase inhibitor which composition comprises lenalidomide, ezatiostat or a salt thereof, and optionally a pharmaceutically acceptable excipient.
  • the ezatiostat or the salt thereof and the lenalidomide together are in a therapeutically effective amount.
  • the composition comprises about 5 mg, 10 mg, 15 mg or 25 mg of lenalidomide and about 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 700 mg, 800 mg, 900 mg, or 1000 mg ezatiostat or a salt thereof.
  • lenalidomide may be added to a tablet formulation of ezatiostat or a salt thereof.
  • a tablet formulation is disclosed in U.S. Patent
  • this invention provides a kit for the treatment of MDS in a patient who has been treated with a DNA methyltransferase inhibitor, which kit comprises a first composition comprising lenalidomide and a second composition comprising ezatiostat or a salt thereof, including those described herein.
  • the ezatiostat or the salt thereof and the lenalidomide together are in a therapeutically effective amount.
  • the kit further comprises a label with instructions to administer the first dose of lenalidomide 1 day, 2 days, 3 days, 4 days, 5 days, 6 days before the first administration of ezatiostat or a salt thereof.
  • the kit further comprises a label with instructions to administer lenalidomide 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, or 6 weeks before administration of ezatiostat or a salt thereof. In some embodiments, the kit further comprises a label with instructions to administer lenalidomide concurrently with ezatiostat or a salt thereof. In some embodiments, the kit further comprises a label with instructions to administer lenalidomide and ezatiostat or a salt thereof according to any of the dosing schedules described herein.
  • the median age was 72 years, with a patient population distribution of IPSS low risk (23 patients, 32 %) and intermediate- 1 risk (50 patients, 68 %). Patients had received a median of three prior MDS therapies including, 34 patients (47 %) with prior Revlimid® (lenalidomide) and 28 patients (38 %) with prior DNA methyltransferase inhibitors (DMTI) [azacitidine, decitabine].
  • DMTI DNA methyltransferase inhibitors
  • HI-N Hematologic Improvement - Neutrophil
  • Telintra® treatment may result in clinically significant hematologic improvement in patients with MDS and may offer an alternative to RBC transfusions. These results are consistent with levels of efficacy observed in prior studies with Telintra®, the first GST Pl-1 enzyme inhibitor tested in MDS patients. [0072] Tables 1 and 2 summarize the results of this clinical study. Table 1
  • Table 2 shows that: (1) when Telintra® was given to patients with no prior treatment of either Revlimid® or a DMTI, the response rate to Telintra® was about 22 %; (2) when Telintra® was given to patients with prior DMTI treatment, none of the patients responded to Telintra®; and (3) the response rate to Telintra® was about 20 % for patients who were treated with both Revlimid® and a DMTI prior to treatment with Telintra®.

Abstract

La présente invention concerne des compositions et des procédés de traitement du syndrome myélodysplasique. Dans un mode de réalisation, la présente invention concerne des procédés de traitement du syndrome myélodysplasique utilisant du ézatiostat ou un sel de celui-ci chez des patients qui ont été traités par un inhibiteur d'ADN méthyltransférase par le biais d'une combinaison d'ézatiostat ou d'un sel de celui-ci et de lénalidomide.
PCT/US2011/046316 2011-08-02 2011-08-02 Compositions et procédés de traitement du syndrome myélodysplasique WO2013019220A1 (fr)

Priority Applications (2)

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PCT/US2011/046316 WO2013019220A1 (fr) 2011-08-02 2011-08-02 Compositions et procédés de traitement du syndrome myélodysplasique
IL230690A IL230690A0 (en) 2011-08-02 2014-01-28 Preparations and methods for the treatment of myelodysplastic syndrome

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PCT/US2011/046316 WO2013019220A1 (fr) 2011-08-02 2011-08-02 Compositions et procédés de traitement du syndrome myélodysplasique

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4113611A (en) 1976-11-16 1978-09-12 Westinghouse Electric Corp. Magnetic pipe cleaner
US5763570A (en) 1987-10-13 1998-06-09 Terrapin Technologies, Inc. Glutathione analogs and paralog panels comprising glutathione mimics
US7029695B2 (en) 2001-07-10 2006-04-18 Telik, Inc. Therapeutic compositions containing glutathione analogs
US7511611B2 (en) 2006-05-18 2009-03-31 Casella Waste Systems, Inc. Systems for and methods of asset management in a waste management service environment
US10875211B2 (en) 2015-03-12 2020-12-29 Robert Bosch Gmbh Electrical configuration for object detection system in a saw

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4113611A (en) 1976-11-16 1978-09-12 Westinghouse Electric Corp. Magnetic pipe cleaner
US5763570A (en) 1987-10-13 1998-06-09 Terrapin Technologies, Inc. Glutathione analogs and paralog panels comprising glutathione mimics
US7029695B2 (en) 2001-07-10 2006-04-18 Telik, Inc. Therapeutic compositions containing glutathione analogs
US7511611B2 (en) 2006-05-18 2009-03-31 Casella Waste Systems, Inc. Systems for and methods of asset management in a waste management service environment
US10875211B2 (en) 2015-03-12 2020-12-29 Robert Bosch Gmbh Electrical configuration for object detection system in a saw

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
ANONYMOUS: "Dose-Ranging Study of Telintra Tablets + Revlimid in Patients With Non-Deletion (5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)", INTERNET CITATION, pages 1 - 5, XP002651698, Retrieved from the Internet <URL:http://clinicaltrials.gov/ct2/show/NCT01062152?term=ezatiostat&rank=2> [retrieved on 20110720] *
ANONYMOUS: "Telik initiates phase I trial of ezatiostat in patients with myelodysplastic syndrome", INTERNET CITATION, 27 January 2010 (2010-01-27), pages 1, XP002651699, Retrieved from the Internet <URL:https://integrity.thomson-pharma.com/integrity/xmlxsl/pk_ref_list.xml _show_ficha_ref?p_ref_id=1444034> [retrieved on 20110720] *
ANONYMOUS: "Telik report phase II data on ezatiostat in MDS", INTERNET CITATION, 9 June 2010 (2010-06-09), pages 1, XP002651700, Retrieved from the Internet <URL:https://integrity.thomson-pharma.com/integrity/xmlxsl/pk_ref_list.xml _show_ficha_ref?p_ref_id=1513842> [retrieved on 20110720] *
LYKO F, BROWN R., J. NATL. CANCER INST., vol. 97, no. 20, 2005, pages 1498 - 506
QUDDUS ET AL., JOURNAL OF HEMATOLOGY & ONCOLOGY, vol. 3, 23 April 2010 (2010-04-23), pages 16
QUDDUS, J. HEM. AND ONC., vol. 3, April 2010 (2010-04-01), pages 15
RAZA AZRA ET AL: "Phase 2 Randomized Multicenter Study of Extended Dosing Schedules of Oral Ezatiostat HCl (Telintra), a Glutathione Analog Prodrug GSTP1-1 Inhibitor, In Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)", BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 116, no. 21, 1 November 2010 (2010-11-01), pages 1198, XP009150424, ISSN: 0006-4971 *
RAZA ET AL., BLOOD, vol. 113, 27 April 2009 (2009-04-27), pages 6533 - 6540
RAZA ET AL., JOURNAL OF HEMATOLOGY & ONCOLOGY, vol. 2, 13 May 2009 (2009-05-13), pages 20

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