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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Nordic MDS Group.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Nordic MDS Group
ClinicalTrials.gov Identifier:
NCT01556477
First received: March 12, 2012
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Acute Myelogenous Leukemia
Drug: Azacitidine
Drug: azacitidine + lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Nordic MDS Group:

Primary Outcome Measures:
  • Response according to IWG criteria for MDS and AML [ Time Frame: 25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Cytogenetic response after 3 cycles using Fluorescence In Situ Hybridization(FISH) [ Time Frame: 25-44 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 72
Study Start Date: March 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556477

Contacts
Contact: Lars Möllgård, MD, PhD +46 8 5858 0000 lars.mollgard@karolinska.se
Contact: Bengt Rasmussen, MD +46 19 6021111 bengt.rasmussen@orebroll.se

Locations
Sweden
Lars Möllgård Recruiting
Stockholm, Sweden, 141 86
Sponsors and Collaborators
Nordic MDS Group
Investigators
Principal Investigator: Lars Möllgård, MD, PhD Nordic MDS Group
  More Information

Additional Information:
No publications provided

Responsible Party: Nordic MDS Group
ClinicalTrials.gov Identifier: NCT01556477     History of Changes
Other Study ID Numbers: NMDSG10B, 2011-001639-21
Study First Received: March 12, 2012
Last Updated: March 14, 2012
Health Authority: Sweden: Medical Products Agency

Keywords provided by Nordic MDS Group:
MDS
AML
Azacitidine
Lenalidomide
del5q

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Azacitidine
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 23, 2014