The Efficacy of Azacitidine +/- Lenalidomide in High-risk Myelodysplastic Syndrome (MDS)and Acute Myeloid Leukemia (AML) With Del(5q).
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| ClinicalTrials.gov Identifier: NCT01556477 |
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Recruitment Status : Unknown
Verified March 2012 by Nordic MDS Group.
Recruitment status was: Recruiting
First Posted : March 16, 2012
Last Update Posted : March 16, 2012
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Myelodysplastic Syndrome Acute Myelogenous Leukemia | Drug: Azacitidine Drug: azacitidine + lenalidomide | Phase 2 |
This is an prospective open multi-center randomized phase II study of standard dose azacytidine with or without the addition of lenalidomide in high-risk myeloid disease (high-risk MDS and AML) with a karyotype including del(5q). Seventy-two patients, eligible for treatment with azacytidine (Intermedium/INT-2 and High-risk MDS and AML with 20-30 % marrow blasts according to label) will be included.
Azacytidine will be given in a modified standard dose, azacytidine 5+2 (75 mg/m2/ d subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacytidine 75 mg/m2/ d for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Cycle interval may be prolonged if toxicity according to predefined criteria occurs. Patients will be randomized to azacytidine (Arm A) or azacytidine + lenalidomide (Arm B). The initial dose of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacytidine cycle and leaving the last week before start of next azacytidine cycle free. The dose should be increased to 20 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. The total study period is 24 weeks + additional weeks caused by prolonged cycle interval. Patients, who following a response may be eligible for allo-SCT may exit the study after cycle 3, 4 or 5 and then be subject to end-of-study assessment. Patients who at start of treatment, or any time during study have a neutrophil count <0,5 x 109/l will be treated with Granulocyte-ColonyStimulatingFactor (G-CSF).
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 72 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q) |
| Study Start Date : | March 2012 |
| Estimated Primary Completion Date : | July 2014 |
| Estimated Study Completion Date : | November 2014 |
| Arm | Intervention/treatment |
|---|---|
| Active Comparator: azacitidine |
Drug: Azacitidine
Azacitidine 5-2-2 (75 mg/m2/day subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacitidine 75 mg/m2/ day for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles.
Other Name: Vidaza |
| Experimental: azacitidine + lenalidomide |
Drug: azacitidine + lenalidomide
Azacitidine 5-2-2 (75 mg/m2/day subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacitidine 75 mg/m2/ day for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Initial dose of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacitidine cycle and leaving the last week before start of next azacitidine cycle free. The dose should increased to 25 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. Total treatment period is 24 weeks. Other Name: Vidaza and Revlimid |
- Response according to IWG criteria for MDS and AML [ Time Frame: 25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide) ]Response according to IWG criteria include hematologic response (including transfusion independence), bone marrow response (blast count) and cytogenetic response (karyotype) after 6 cycles of azacytidine or azacytidine+lenalidomide. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
- Cytogenetic response after 3 cycles using Fluorescence In Situ Hybridization(FISH) [ Time Frame: 25-44 weeks ]After 3 cycles the 5q- clone will be measured with FISH to see if there is a response already at that time. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
- Safety (number and types of adverse advents) in azacitidine vs azacitidine + lenalidomide groups [ Time Frame: 25-44 weeks ]Heamtological adverse events will be monitored by checking Hemoglobin,Leucocyte count, Platelet and a Differential every week. Non-Hematological adverse events will be monitored and reported in the Case report form (CRF). For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
- Azacitidine cycle interval between groups [ Time Frame: 25-44 weeks ]For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
- Survival in azacitidine vs azacitidine + lenalidomide groups [ Time Frame: Up to week 156 ]All patients will undergo follow-up once yearly from start of treatment; week 52, 104, and 156.
- Relapse in azacitidine vs azacitidine + lenalidomide groups [ Time Frame: Up to week 156 ]All patients will undergo follow-up once yearly from start of treatment; week 52, 104, and 156.
- Analysis of a broad spectrum of molecular and cellular events which previously have been identified as related to MDS with del(5q). [ Time Frame: 25-44 weeks ]Bone marrow will be biobanked at inclusion and after 6 cycles of treatment or or at end of study if this occurs at an earlier time point. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 18 years of age at the time of signing the informed consent form.
- MDS with IPSS Int-2 or High with a karyotype including del(5q).
- Acute myeloid leukaemia (AML) with multilineage dysplasia and 20-30 % blasts (former RAEB-t) with a karyotype including del(5q).
- Subject has signed the informed consent form.
- Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test prior to starting lenalidomide. In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, patches, or implantable hormonal contraceptive methods; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on lenalidomide. WCBP must agree to have pregnancy tests every 4 weeks while on lenalidomide.
- Males (including those who have had a vasectomy) must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with WCBP while on lenalidomide, when temporarily stopping lenalidomide and 28 days after the last dose of lenalidomide.
Note: Refractory and relapsed patients can be included as long as they fulfil the inclusion criteria.
Exclusion Criteria:
- Eligible for upfront allogeneic SCT without prior induction chemotherapy or azacitidine
- Pregnant or lactating females.
- Prior therapy with azacitidine
- Prior therapy with lenalidomide
- Expected survival less than two months.
- Acute promyelocytic leukemia (APL)
- Central nervous system leukemia
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Serum biochemical values as follows
- Serum creatinine >2.0 mg/dL (177 mmol/L)
- Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transferase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)
- Serum total bilirubin >1.5 mg/dL
- Prior allergic reaction to thalidomide
- Uncontrolled systemic infection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01556477
| Contact: Lars Möllgård, MD, PhD | +46 8 5858 0000 | lars.mollgard@karolinska.se | |
| Contact: Bengt Rasmussen, MD | +46 19 6021111 | bengt.rasmussen@orebroll.se |
| Sweden | |
| Lars Möllgård | Recruiting |
| Stockholm, Sweden, 141 86 | |
| Principal Investigator: | Lars Möllgård, MD, PhD | Nordic MDS Group |
Additional Information:
| Responsible Party: | Nordic MDS Group |
| ClinicalTrials.gov Identifier: | NCT01556477 History of Changes |
| Other Study ID Numbers: |
NMDSG10B 2011-001639-21 ( EudraCT Number ) |
| First Posted: | March 16, 2012 Key Record Dates |
| Last Update Posted: | March 16, 2012 |
| Last Verified: | March 2012 |
Keywords provided by Nordic MDS Group:
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MDS AML Azacitidine Lenalidomide del5q |
Additional relevant MeSH terms:
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Syndrome Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Disease Pathologic Processes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions |
Lenalidomide Azacitidine Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors |