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| ID | Type | Description | Link |
|---|---|---|---|
| ULEU13049 | Other Identifier | University of Rochester |
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To evaluate the response to chemotherapy with the drug decitabine combined with rapamycin in the treatment of relapsed or refractory acute myeloid leukemia in patients of all ages, and in the treatment of newly diagnosed leukemia in those who are older than 65 when diagnosed.
To determine the efficacy of decitabine followed by Rapamycin in previously untreated elderly patients not able to receive standard chemotherapy or in patients with relapsed or refractory AML, through measurement of Complete Remission (CR), Complete Remission Incomplete Platelet Recovery (CRp), Partial Remission (PR), and event free and overall survival (Arm A).
To determine the safety of administration of decitabine with escalating doses of Ribavirin in elderly leukemia patients or patients with relapsed/refractory disease with M4/M5 subtypes anticipated to express high eukaryotic translation initiation factor 4E (eIF4E) at diagnosis (Arm B).
To establish effect of these sequential treatments on expression of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt /mTOR) pathway proteins and on eukaryotic translation initiation factor 4E (eIF4E) activation through Western blot and phospho-flow methodologies.
To correlate the clinical response with baseline expression of phospho-p70S6 Kinase/phosphorylated protein kinase B (pAKT) and with the in vitro inhibitory effects of mammalian target of rapamycin (mTOR) inhibition with rapamycin or ribavirin on the level of downstream effectors.
To determine whether a leukemia stem cell phenotype is inhibited by the sequential administration of decitabine/rapamycin or decitabine/ribavirin.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Decitabine followed by rapamycin | Experimental | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes). |
|
| Decitabine followed by ribavirin | Experimental | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Decitabine | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Median Overall Survival | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Blast Percentage in Peripheral Blood | bone marrow aspirate and biopsy exam | baseline and four weeks |
| Mean Change in Blast Percentage in Marrow | Complete blood count with differential. |
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Inclusion Criteria:
4.1.1 Age >/= 18 4.1.2 Diagnosis of AML according to World Health Organization (WHO) criteria except acute promyelocytic leukemia AND 4.1.3 Refractory AML defined as failure to achieve Complete Remission (CR) after 2 cycles of induction chemotherapy or persistence of > 40% bone marrow blasts after one cycle of chemotherapy induction OR 4.1.4 Relapsed AML defined as any evidence of disease recurrence after achieving a documented first or greater Complete Remission (CR) OR 4.1.5 Relapsed AML after stem cell transplantation. 90 days (since stem cell infusion) must have elapsed between transplant and emergence of recurrent AML OR 4.1.6 Newly diagnosed AML in a patient >65 years old not considered fit for standard 7+ 3 chemotherapy or who declines such therapy after discussion of therapeutic options available.
4.1.7 Eastern Cooperative Oncology Group (ECOG) performance status <3
Exclusion Criteria:
4.2.1 Abnormal renal function as evidenced by a calculated creatinine clearance ≤ 30 ml/min (Cockcroft-Gault formula (Appendix 2) 4.2.2 Abnormal liver function: Bilirubin >2.0 mg/dl, transaminase(s) more than 2.5x the upper limits of normal 4.2.3 Active systemic infection not responding to antibiotics 4.2.4 Known diagnosis of human immunodeficiency virus infection (HIV) 4.2.5 Patients who are post-allogeneic transplantation should not have active Graft vs. Host Disease (GVHD) greater than grade 1 of skin at time of enrollment. They may have had donor lymphocyte infusion (DLI) but not within 4 weeks of beginning the study.
4.2.6 Pregnant or breastfeeding female subjects 4.2.7 Known or suspected Central Nervous System (CNS) leukemia involvement; past involvement is not an exclusion.
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| Name | Affiliation | Role |
|---|---|---|
| Jane Liesveld, MD | University of Rochester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Rochester | Rochester | New York | 14642 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34839054 | Derived | Liesveld JL, Baran A, Azadniv M, Misch H, Nedrow K, Becker M, Loh KP, O'Dwyer KM, Mendler JH. A phase II study of sequential decitabine and rapamycin in acute myelogenous leukemia. Leuk Res. 2022 Jan;112:106749. doi: 10.1016/j.leukres.2021.106749. Epub 2021 Nov 11. |
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37 patients signed consent for the study and 27 patients enrolled. Reasons for non-enrollment were withdrawal of consent (3 patients), diagnosis of MDS vs. AML on screening marrow (2 patients), enrollment on an alternate clinical trial (4 patients), and expiration during screening period due to sepsis (1 patient). The first patient enrolled in March 2014 and the last in January 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Decitabine Followed by Rapamycin | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes). Decitabine |
| FG001 | Decitabine Followed by Ribavirin | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes). Decitabine |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Decitabine Followed by Rapamycin | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes). Decitabine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Median Overall Survival | The Ribavirin arm did not complete the study and entered hospice before 4 weeks. Median survival of the rapamycin arm included all 26 participant who started the study. | Posted | Median | 95% Confidence Interval | months | 2 years |
|
2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Decitabine Followed by Rapamycin | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes). Decitabine |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoptysis | Respiratory, thoracic and mediastinal disorders | CTAE version 4.03 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| alkaline phosphatase increased | Hepatobiliary disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jane Liesveld | University of Rochester | 585 - 275 - 5823 | Jane_Liesveld@urmc.rochester.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 9, 2017 | May 18, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 1, 2019 | May 18, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077209 | Decitabine |
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
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| baseline and four weeks |
| BG001 | Decitabine Followed by Ribavirin | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes). Decitabine |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|
| Secondary | Blast Percentage in Peripheral Blood | bone marrow aspirate and biopsy exam | Data was not collected for two patients in the rapamycin arm and 1 patient in the ribavirin arm. | Posted | Mean | Standard Deviation | percentage of cells | baseline and four weeks |
|
|
|
| Secondary | Mean Change in Blast Percentage in Marrow | Complete blood count with differential. | Data was not collected for two patients in the rapamycin arm and 1 patient in the ribavirin arm. | Posted | Mean | Full Range | percentage of cells | baseline and four weeks |
|
|
|
| 25 |
| 26 |
| 21 |
| 26 |
| 26 |
| 26 |
| EG001 | Decitabine Followed by Ribavirin | Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes). Decitabine | 1 | 1 | 1 | 1 | 1 | 1 |
| pneumonia | Infections and infestations | CTAE version 4.03 | Non-systematic Assessment |
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| syncope | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Intracranial hemorrhage | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Gastric hemorrhage | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| decreased platelet count | Blood and lymphatic system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| skin infection | Infections and infestations | CTAE version 4.03 | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | CTAE version 4.03 | Non-systematic Assessment |
|
| Chest pain | General disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Diverticulitis | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Mucositis | Respiratory, thoracic and mediastinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Multi-organ failure | General disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTAE version 4.03 | Non-systematic Assessment |
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| Confusion | Psychiatric disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | CTAE version 4.03 | Non-systematic Assessment |
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| Hallucinations | Psychiatric disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Hypertension | Vascular disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Infection | Infections and infestations | CTAE version 4.03 | Non-systematic Assessment |
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| Lethargy | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Peripheral Neuropathy | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Pruritis | Skin and subcutaneous tissue disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Rhinitis/sinusitis | Infections and infestations | CTAE version 4.03 | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Fatigue | General disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Edema | General disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Fever | General disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Skin infection | Infections and infestations | CTAE version 4.03 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | CTAE version 4.03 | Non-systematic Assessment |
|
| Chills | General disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| GI discomfort | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| ALT increased | Hepatobiliary disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Anxiety | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Bleeding from central line | Blood and lymphatic system disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Extremity pain | Musculoskeletal and connective tissue disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Malaise | General disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Sore throat | Gastrointestinal disorders | CTAE version 4.03 | Non-systematic Assessment |
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| Decreased platelets | Blood and lymphatic system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Pain | General disorders | CTAE version 4.03 | Non-systematic Assessment |
|
| Sepsis | Immune system disorders | CTAE version 4.03 | Non-systematic Assessment |
|
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| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D011741 |
| Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |