The Efficacy of Azacitidine +/- Lenalidomide in High-risk Myelodysplastic Syndrome (MDS)and Acute Myeloid Leukemia (AML) With Del(5q).

NCT ID: NCT01556477

Last Updated: 2012-03-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2014-11-30

Brief Summary

The proposed phase II trial is a multicenter, randomized, open-label study that will evaluate the efficacy and safety of azacitidine alone or in combination with lenalidomide in high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) with a karyotype including del(5q). The primary objective will be to evaluate the efficacy in terms of response according to International Working Group (IWG) criteria for MDS and AML after 6 cycles of azacitidine or azacitidine + lenalidomide treatment, or at end of study if this occurs at an earlier time point.

Detailed Description

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).

Conditions

Myelodysplastic Syndrome; Acute Myelogenous Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

azacitidine

Group Type: ACTIVE_COMPARATOR

Azacitidine

Intervention Type: DRUG

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.

azacitidine + lenalidomide

Group Type: EXPERIMENTAL

azacitidine + lenalidomide

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Vidaza; Vidaza and Revlimid

Eligibility Criteria

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.

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
• Serum biochemical values as follows

1. Serum creatinine >2.0 mg/dL (177 mmol/L)

2. 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)

3. Serum total bilirubin >1.5 mg/dL

• Prior allergic reaction to thalidomide
• Uncontrolled systemic infection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nordic MDS Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lars Möllgård, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nordic MDS Group

Locations

Lars Möllgård

Stockholm, , Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Lars Möllgård, MD, PhD

Role: CONTACT

lars.mollgard@karolinska.se

+46 8 5858 0000

Bengt Rasmussen, MD

Role: CONTACT

bengt.rasmussen@orebroll.se

+46 19 6021111

References

Rasmussen B, Nilsson L, Tobiasson M, Jadersten M, Garelius H, Dybedal I, Gronbaek K, Ejerblad E, Lorenz F, Flogegard M, Marcher CW, Cavalier L, Ebeling F, Olsnes AM, Norgaard JM, Saft L, Mollgard L, Hellstrom-Lindberg E, Schlegelberger B, Gohring G. Influence of Cytogenetics on the Outcome of Patients With High-Risk Myelodysplastic Syndrome Including Deletion 5q Treated With Azacitidine With or Without Lenalidomide. Genes Chromosomes Cancer. 2025 Feb;64(2):e70029. doi: 10.1002/gcc.70029.

Reference Type: DERIVED

PMID: 39921387 (View on PubMed)

Related Links

http://www.nmds.org

Nordic MDS Group website

Other Identifiers

2011-001639-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NMDSG10B

Identifier Type: -

Identifier Source: org_study_id