thalidomide and Refractory Anemia studies

Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.
2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.

Research Excerpts

Excerpt	Relevance	Reference
"Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy."	9.11	Efficacy of lenalidomide in myelodysplastic syndromes. ( Buresh, A; Fuchs, D; Heaton, R; Knight, R; Kurtin, S; List, A; Mahadevan, D; Rimsza, L; Roe, DJ; Zeldis, JB, 2005)
"Existing studies regarding the role of DNA methyltransferase inhibitors (DNMTi) and lenalidomide in refractory anemia with ring sideroblasts (RARS) are limited."	8.02	Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States. ( Bewersdorf, JP; Gore, SD; Huntington, SF; Ma, X; Podoltsev, NA; Wang, R; Wang, X; Zeidan, AM; Zhang, C, 2021)
"We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA."	7.71	Thalidomide for the treatment of patients with myelodysplastic syndromes. ( Aivado, M; Gattermann, N; Germing, U; Haas, R; Misgeld, E; Strupp, C, 2002)
"The myelodysplastic syndromes are a heterogeneous group of clonal diseases of haemopoiesis, which are a challenge for both biologists and clinicians."	6.41	Thalidomide in myelodysplastic syndromes. ( Pozzato, G; Zorat, F, 2002)
"As lenalidomide has shown to be efficacious in both myelodysplastic syndromes and myeloproliferative neoplasms, we have treated 2 RARS-T patients, who were transfusion dependent, with lenalidomide."	5.36	Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis. ( de Wolf, JT; Huls, G; Mulder, AB; Rosati, S; van de Loosdrecht, AA; Vellenga, E, 2010)
"Lenalidomide has hematologic activity in patients with low-risk myelodysplastic syndromes who have no response to erythropoietin or who are unlikely to benefit from conventional therapy."	5.11	Efficacy of lenalidomide in myelodysplastic syndromes. ( Buresh, A; Fuchs, D; Heaton, R; Knight, R; Kurtin, S; List, A; Mahadevan, D; Rimsza, L; Roe, DJ; Zeldis, JB, 2005)
"Existing studies regarding the role of DNA methyltransferase inhibitors (DNMTi) and lenalidomide in refractory anemia with ring sideroblasts (RARS) are limited."	4.02	Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States. ( Bewersdorf, JP; Gore, SD; Huntington, SF; Ma, X; Podoltsev, NA; Wang, R; Wang, X; Zeidan, AM; Zhang, C, 2021)
"We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA."	3.71	Thalidomide for the treatment of patients with myelodysplastic syndromes. ( Aivado, M; Gattermann, N; Germing, U; Haas, R; Misgeld, E; Strupp, C, 2002)
"Anemia and iron overload are complications in both diseases and are managed similar to lower risk MDS."	2.52	Refractory anemia with ring sideroblasts and RARS with thrombocytosis. ( Patnaik, MM; Tefferi, A, 2015)
"MDS with trisomy 8 has been observed in adult patients with Behçet syndrome with some cases developing prior to the clinical manifestations of the latter."	2.44	Myelodysplastic syndrome with trisomy 8 associated with Behçet syndrome: an immunologic link to a karyotypic abnormality. ( Bolton-Maggs, P; Field, A; Moots, R; Salim, R; Thachil, JV, 2008)
"The myelodysplastic syndromes are a heterogeneous group of clonal diseases of haemopoiesis, which are a challenge for both biologists and clinicians."	2.41	Thalidomide in myelodysplastic syndromes. ( Pozzato, G; Zorat, F, 2002)
"As lenalidomide has shown to be efficacious in both myelodysplastic syndromes and myeloproliferative neoplasms, we have treated 2 RARS-T patients, who were transfusion dependent, with lenalidomide."	1.36	Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis. ( de Wolf, JT; Huls, G; Mulder, AB; Rosati, S; van de Loosdrecht, AA; Vellenga, E, 2010)
"Treatment with thalidomide, 50-150 mg/d, and prednisolone, 25 mg/d, resulted in an increase in haemoglobin to 8."	1.33	[Refractory anaemia successfully treated with thalidomide]. ( Hansen, M; Hansen, PB, 2006)

Research

Studies (13)

Authors

Clinical Trials (6)

Trial Overview

Trial Outcomes

Complete Response

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	7 (53.85)	29.6817
2010's	5 (38.46)	24.3611
2020's	1 (7.69)	2.80

Authors	Studies
Wang, X	1
Zeidan, AM	1
Wang, R	1
Bewersdorf, JP	1
Zhang, C	1
Podoltsev, NA	1
Huntington, SF	1
Gore, SD	1
Ma, X	1
Caers, J	1
Hafraoui, K	1
Keutgens, A	1
Caberg, JH	1
Lambert, F	1
Tassin, F	1
Beguin, Y	1
Patnaik, MM	1
Tefferi, A	1
Huls, G	1
Mulder, AB	1
Rosati, S	1
van de Loosdrecht, AA	1
Vellenga, E	1
de Wolf, JT	1
Ziarkiewicz, M	1
Dwilewicz-Trojaczek, J	1
Pastwińska, A	1
Chmarzyńska, E	1
Paszkowska-Kowalewska, M	1
Koperski, Ł	1
Jędrzejczak, WW	1
Ziarkiewicz-Wróblewska, B	1
Zhang, M	1
You, Y	1
Li, X	1
He, Y	1
Zheng, J	1
Li, W	1
Zou, P	1
Liu, X	1
Liu, F	1
List, A	1
Kurtin, S	1
Roe, DJ	1
Buresh, A	1
Mahadevan, D	1
Fuchs, D	1
Rimsza, L	1
Heaton, R	1
Knight, R	1
Zeldis, JB	1
Hansen, M	1
Hansen, PB	1
Dunne, KA	1
Hill, J	1
Dillon, JF	1
Thachil, JV	1
Salim, R	1
Field, A	1
Moots, R	1
Bolton-Maggs, P	1
Kelaidi, C	1
Eclache, V	1
Fenaux, P	1
Strupp, C	1
Germing, U	1
Aivado, M	1
Misgeld, E	1
Haas, R	1
Gattermann, N	1
Zorat, F	1
Pozzato, G	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Multicenter, Randomized, Double-blind, Phase III Study of REVLIMID (Lenalidomide) Versus Placebo in Patients With Low Risk Myelodysplastic Syndrome (Low and Intermediate-1 IPSS) With Alteration in 5q- and Anemia Without the Need of Transfusion.[NCT01243476]	Phase 3	61 participants (Actual)	Interventional	2010-01-31	Completed
Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated CLL With Four or Six Cycles of Fludarabine and Cyclophosphamide With Rituximab (FCR) Plus Lenalidomide Followed by Lenalidomide Consolidation/ Maintenance[NCT01723839]	Phase 2	21 participants (Actual)	Interventional	2012-02-22	Completed
A Phase II Open Label Study of the Safety and Efficacy of CC-5013 Treatment For Patients With Myelodysplastic Syndrome[NCT00044382]	Phase 2	25 participants	Interventional	2002-02-01	Completed
Salvage in Patients With Myelodysplastic Syndrome After Failure of Hypomethylating Agents: Lenalidomide as a Second-line Therapy[NCT01673308]	Phase 2	35 participants (Anticipated)	Interventional	2012-08-31	Active, not recruiting
A Phase I/II Study of Bendamustine, Lenalidomide and Low-dose Dexamethasone, (BdL) for the Treatment of Patients With Relapsed Myeloma.[NCT01686386]	Phase 1/Phase 2	60 participants (Anticipated)	Interventional	2010-02-28	Recruiting
Phase II Trial of Lenalidomide in Older Patients (>/= 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities[NCT00546897]	Phase 2	48 participants (Actual)	Interventional	2007-02-28	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Analysis of the Primary Endpoint: The complete responses will be estimated by the number of patients with CR divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 4 cycles

Overall Response Rate

Intervention	Percentage of Participants (Number)
FCR With Lenalidomide	45

Analysis of the other Secondary Endpoints: The overall response rate will be estimated by the number of patients with complete and partial responses divided by the total number of evaluable patients. (NCT01723839)
Timeframe: 28 day cycle, up to 6 cycles

CR With Complete Blood Counts (CRi) Rate

Intervention	Percentage of Participants (Number)
FCR With Lenalidomide	95

CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Cytogenetics CR Rate (CRc)

Intervention	participants (Number)
Cohort 1	0
Cohort 2	4

Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells). (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Duration of CR for Complete Responders

Intervention	participants (Number)
Cohort 1	1
Cohort 2	3

Duration of remission: Defined as the interval from the date complete remission is documented to the date of recurrence (NCT00546897)
Timeframe: 2 years

Morphologic Complete Remission Rate (CRm)

Intervention	months (Median)
Cohort 2	10

CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Morphologic Leukemia Free State

Intervention	participants (Number)
Cohort 1	0
Cohort 2	3

Morphologic leukemia-free state: Defined as < 5% blasts on the BM aspirate with spicules and a count of > 200 nucleated cells and no blasts with Auer rods, and no persistent extramedullary disease. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Overall Survival (OS)

Intervention	participants (Number)
Cohort 1	1
Cohort 2	10

Overall survival: Defined as the date of first dose of study drug to the date of death from any cause. (NCT00546897)
Timeframe: 2 years

Partial Remission Rate (PR)

Intervention	months (Median)
Cohort 2	4

Partial remission (PR): Requires that the criteria for complete remission be met with the following exceptions: decrease of >50% in the percentage of blasts to 5-25% in the BM aspirate. A value of < 5% blasts in BM with Auer rods is also considered a partial remission. (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Progression-free Survival

Intervention	participants (Number)
Cohort 1	1
Cohort 2	0

Progression-free survival (PFS) denotes the chances of staying free of disease progression for a group of individuals suffering from a cancer after a particular treatment. It is the percentage of individuals in the group whose disease is likely to remain stable (and not show signs of progression) after a specified duration of time. Progression-free survival rates are an indication of how effective a particular treatment is. (NCT00546897)
Timeframe: 2 years

Relapse Free Survival (RFS) for Complete Responders

Intervention	months (Median)
Cohort 2	2

This is determined only for patients achieving a complete remission. Defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause. (NCT00546897)
Timeframe: 2 years

Safety and Tolerability (Removal From Study Due to Adverse Events)

Intervention	months (Median)
Cohort 2	10

Toxicity will be scored using CTCAE Version 3.0 for toxicity and adverse event reporting (NCT00546897)
Timeframe: 4 weeks after last dose of study drug [median duration of therapy was 65 days (range, 3-413 days)]

Complete Remission Rate (CRm + CRi + CRc)

Intervention	participants (Number)
Cohort 1	1
Cohort 2	8

"CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count >100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.~CRi = Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.~Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells)." (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Response Rate (RR)

Intervention	participants (Number)
	CRm	CRi	CRc
Cohort 1	0	0	1
Cohort 2	3	4	3

"RR = as patients obtaining any response (CRm + CRc +CRi + PR).~CRm = Defined as morphologic leukemia-free state, including <5% blasts in BM aspirate with marrow spicules and a count of > 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC > 1000/uL, platelet count > 100,000/uL. Patient must be independent of transfusions for a minimum of 1 week before each marrow assessment. There is no duration requirement for this designation.~CRc = Cytogenetic complete remission (CRc): Only patients with an identified cytogenetic abnormality may receive this designation. Defines as a morphologic complete remission plus reversion to a normal karyotype (no clonal abnormalities detected in a minimum of 20 mitotic cells).~Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia <1000/uL or thrombocytopenia <100,000/ul.~Partial remission (PR): Requires" (NCT00546897)
Timeframe: After 2 cycles of low dose lenalidomide (approximately Day 113 for Cohort 1 and approximately Day 104 for Cohort 2)

Article	Year
Clinical effectiveness of DNA methyltransferase inhibitors and lenalidomide in older patients with refractory anemia with ring sideroblasts: a population-based study in the United States. Leukemia & lymphoma, 2021, Volume: 62, Issue:10 Topics: Aged; Anemia, Refractory; Chromosome Deletion; Chromosomes, Human, Pair 5; DNA; Humans; Lenalidomide	2021
Haematological and molecular responses in refractory anaemia with ring sideroblasts and thrombocytosis treated with lenalidomide. European journal of haematology, 2014, Volume: 92, Issue:2 Topics: Aged, 80 and over; Anemia, Refractory; Bone Marrow; Erythrocytes, Abnormal; Female; Humans; Immunolo	2014
Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis. Blood, 2010, Jul-15, Volume: 116, Issue:2 Topics: Aged, 80 and over; Anabolic Agents; Anemia, Refractory; Anemia, Sideroblastic; Antineoplastic Agents	2010
Refractory anaemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) with superimposed 5q-syndrome. Polish journal of pathology : official journal of the Polish Society of Pathologists, 2010, Volume: 61, Issue:2 Topics: Aged; Anemia, Macrocytic; Anemia, Refractory; Anemia, Sideroblastic; Antineoplastic Agents; Bone Mar	2010
Response to lenalidomide of a patient with t(2;3)(p23;q29) and JAK2 non-mutated refractory anemia with ring sideroblasts and thrombocytosis. Leukemia & lymphoma, 2013, Volume: 54, Issue:7 Topics: Adult; Anemia, Refractory; Bone Marrow; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 3; Fema	2013
[Refractory anaemia successfully treated with thalidomide]. Ugeskrift for laeger, 2006, Feb-06, Volume: 168, Issue:6 Topics: Anemia, Refractory; Angiogenesis Inhibitors; Drug Therapy, Combination; Hemoglobins; Humans; Immunos	2006
Treatment of chronic transfusion-dependent gastric antral vascular ectasia (watermelon stomach) with thalidomide. European journal of gastroenterology & hepatology, 2006, Volume: 18, Issue:4 Topics: Anemia, Refractory; Angiogenesis Inhibitors; Gastric Antral Vascular Ectasia; Humans; Male; Middle A	2006
Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia, 2002, Volume: 16, Issue:1 Topics: Aged; Aged, 80 and over; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Blood Transf	2002

thalidomide and Refractory Anemia