CompletedNCT00352001Updated Sep 19, 2018Results posted

Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

A Phase 1/2 interventional study of azacitidine and lenalidomide in Leukemia and Myelodysplastic Syndromes, sponsored by Mikkael Sekeres MD. Completed at 3 sites in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2018-09-19.

Sponsored by Mikkael Sekeres MD · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 37
Allocation: Not applicable
Ages: 18 Years to 120 Years
Sex: All

Study summary

RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Lenalidomide may also stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving lenalidomide together with azacitidine may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of lenalidomide and azacitidine in treating patients with advanced myelodysplastic syndromes.

Read the detailed description

OBJECTIVES:

Primary

Determine the maximum tolerated dose and dose-limiting toxicity of lenalidomide and azacitidine in patients with advanced myelodysplastic syndromes (MDS).

Secondary

Review clinical outcomes, as defined by the International Working Group criteria, in patients treated with this regimen.
Determine time to transformation to acute myeloid leukemia or death in patients treated with this regimen.
Determine time to relapse after achieving complete or partial remission in patients treated with this regimen.
Determine time to disease progression in patients treated with this regimen.
Determine the effect of this regimen on hematologic status (including peripheral blood counts and the need for platelet and/or red blood cell transfusions) in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study.

Patients receive oral lenalidomide once daily on days 1-14 or days 1-21 and azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses and/or increasing dosing frequencies of lenalidomide and azacitidine until the maximum tolerated dose (MTD) is determined or the sixth dose level is reached, whichever occurs first. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy.

After completion of study treatment, patients are followed annually.

Conditions studied

Leukemia
Myelodysplastic Syndromes

Browse trials for

Keywords

refractory anemia with excess blasts
previously treated myelodysplastic syndromes
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes

In context

Preleukemia

1,317 studies on the registry are indexed under Preleukemia; 57 are open to participants now.

This study's enrollment of 37 is close to the median of 36 across 1,060 interventional studies indexed under Preleukemia.

Browse Preleukemia studies →

Lead sponsor

This is the only study on the registry with Mikkael Sekeres MD as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

DISEASE CHARACTERISTICS:

Diagnosis of myelodysplastic syndromes (MDS) meeting one of the following criteria:
- French-American-British histological classification criteria
  - Refractory anemia with excess blasts (RAEB), defined as 5-19% myeloblasts in the bone marrow
    - Patients with 20% blasts are considered to have acute myeloid leukemia (per WHO classification system) and are therefore excluded in this study
  - Chronic myelomonocytic leukemia (CMML), defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood
- WHO histological classification criteria
  - RAEB-1, defined as 5-9% myeloblasts in the bone marrow
  - RAEB-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood
  - CMML-2, defined as 10-19% myeloblasts in the bone marrow and/or 5-19% blasts in the blood
- International Prognostic Scoring System (IPSS) score of intermediate 2 (1.5-2.0 points based on karyotype, cytopenias, and bone marrow blast percentage) or high (≥ 2.5 points), in the setting of ≥ 5% myeloblasts
Considered ineligible for bone marrow transplantation as first-line therapy

PATIENT CHARACTERISTICS:

Life expectancy ≥ 3 months
ECOG performance status 0-2
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method contraception for 4 weeks before, during, and for 4 weeks after completion of study treatment
No serious medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the treating physician, would preclude study participation or preclude giving informed consent
No preexisting neurotoxicity or neuropathy ≥ grade 2
No rash or prior hypersensitivity or allergic reaction ≥ grade 3 to thalidomide
Creatinine ≤ 2.0 mg/dL
AST and ALT ≤ 2.0 times upper limit of normal
Bilirubin ≤ 2 mg/dL
Platelet count ≥ 50,000/mm\^3
Absolute neutrophil count ≥ 500/mm\^3
No other malignancy within the past 3 years except curatively treated carcinoma in situ of the cervix or nonmelanoma skin cancer
No history of thromboembolic event or other condition requiring use of anticoagulation with warfarin or low molecular-weight heparin
No known or suspected hypersensitivity to azacitidine or mannitol

PRIOR CONCURRENT THERAPY:

More than 28 days since prior and no other concurrent investigational agents for MDS
More than 28 days since prior approved therapy for MDS
More than 14 days since prior growth factors
More than 28 days since prior and no concurrent supraphysiologic doses (equivalent to > 10 mg/day of prednisone) of corticosteroids
More than 12 months since prior radiotherapy, chemotherapy, or cytotoxic therapy for treatment of conditions other than MDS
No prior lenalidomide or azacitidine
No prior stem cell or bone marrow transplantation
No concurrent androgens, epoetin alfa, or chemotherapy for MDS

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 37 participants (actual)

Study arms

Experimental
Lenalidomide and Azacitidine
Drug: azacitidine · Drug: lenalidomide

Interventions

Drugazacitidine
Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Also known as: Vidaza®
Druglenalidomide
Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.
Also known as: Revlimid®

What researchers measure

Primary outcomes

PHASE I: Maximum Tolerated Dose of Azacitidine
Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
Time frame: After 1 courses (1 months)
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement. Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/L
Time frame: After 4 courses (4 months)
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement) Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/L
Time frame: After 7 courses (months)
PHASE I: Maximum Tolerated Dose of Lenalidomide
Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
Time frame: After 1 courses (1 months)

Secondary outcomes

Time to Transformation to Acute Myeloid Leukemia or Death
Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria
Time frame: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Time to Relapse After Achieving Complete Response
Time frame: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events
Time frame: After 7 months
Overall Survival Among Patients With Complete Response
Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study
Time frame: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

Results

Posted Sep 19, 2018

Participant flow

Participant flow — Overall Study
Milestone	Lenalidomide and Azacitidine
Started	37
Azacitidine 75mg/lenalidomide 5mg-14 day	3
Azacitidine 75mg/lenalidomide 5mg-21 day	3
Azacitidine 75mg/lenalidomide 10mg-14day	3
Completed	37
Not completed	0

Outcome measures

PrimaryPHASE I: Maximum Tolerated Dose of Azacitidine

Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard "3+3" design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.

Time frame:: After 1 courses (1 months)
Reported as:: Number · mg/m2 subcutaneously for 5 days

PHASE I: Maximum Tolerated Dose of Azacitidine
mg/m2 subcutaneously for 5 days	Lenalidomide and Azacitidine
PHASE I: Maximum Tolerated Dose of Azacitidine	75

PrimaryPHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)

For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement. Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/L

Time frame:: After 4 courses (4 months)
Reported as:: Number · participants

PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
participants	Lenalidomide and Azacitidine
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)	26

PrimaryPHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)

For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement) Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones. Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality. Hematologic Improvement (HI) is defined as: red blood cell increase of \>=1.5g/dL, a platelet response of \>=30X10\^9/L or by at least 100% for values starting \<20X10\^9/L, or a neutrophil response of at least 100% and absolute increase of \>0.5X10\^9/L

Time frame:: After 7 courses (months)
Reported as:: Number · participants

PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
participants	Lenalidomide and Azacitidine
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)	26

SecondaryTime to Transformation to Acute Myeloid Leukemia or Death

Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria

Time frame:: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Reported as:: Median · months

Time to Transformation to Acute Myeloid Leukemia or Death
months	Lenalidomide and Azacitidine
Time to Transformation to Acute Myeloid Leukemia or Death	13.6 (3 to 55)

SecondaryTime to Relapse After Achieving Complete Response

Time frame:: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Reported as:: Median · months

Time to Relapse After Achieving Complete Response
months	Lenalidomide and Azacitidine
Time to Relapse After Achieving Complete Response	17 (3 to 39)

SecondaryNumber of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events

Time frame:: After 7 months
Reported as:: Number · participants

Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events
participants	Lenalidomide and Azacitidine
Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events	9

PrimaryPHASE I: Maximum Tolerated Dose of Lenalidomide

Time frame:: After 1 courses (1 months)
Reported as:: Number · mg orally for 21 days

PHASE I: Maximum Tolerated Dose of Lenalidomide
mg orally for 21 days	Lenalidomide and Azacitidine
PHASE I: Maximum Tolerated Dose of Lenalidomide	10

SecondaryOverall Survival Among Patients With Complete Response

Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study

Time frame:: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Reported as:: Median · months

Overall Survival Among Patients With Complete Response
months	Lenalidomide and Azacitidine
Overall Survival Among Patients With Complete Response	37 (7 to 55)

Adverse events

Collected over 28 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Lenalidomide and Azacitidine	—	10/37 (27%)	37/37 (100%)

Most frequent serious events

Showing 10 of 19

Most frequent serious events
Event	Lenalidomide and Azacitidine
Febrile NeutropeniaBlood and lymphatic system disorders	5/37
Neutrophils/granulocytesInvestigations	2/37
PlateletsInvestigations	2/37
Rash/desquamationSkin and subcutaneous tissue disorders	2/37
Congestive Heart FailureCardiac disorders	1/37
Myocardial InfarctionCardiac disorders	1/37
CNS Hemorrhage/bleedingNervous system disorders	1/37
Deep vein or cardiac thrombosisVascular disorders	1/37
general disorderGeneral disorders	1/37
weakness/dizzinessNervous system disorders	1/37

Most frequent other events

Showing 10 of 39

Most frequent other events
Event	Lenalidomide and Azacitidine
Fatigue (asthenia, lethargy, malaise)General disorders	21/37
ConstipationGastrointestinal disorders	20/37
PainGeneral disorders	19/37
PlateletsInvestigations	18/37
DiarrheaGastrointestinal disorders	18/37
Neutrophils/granulocytes (ANC/AGC)Investigations	17/37
Injection site reaction/extravasation changesGeneral disorders	17/37
HemoglobinBlood and lymphatic system disorders	16/37
Leukocytes (total WBC)Investigations	12/37
Pruritus/itchingSkin and subcutaneous tissue disorders	12/37

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Lenalidomide and Azacitidine
Median	76.5 (54 to 88)

Sex: Female, Male
Sex: Female, Male(Participants)	Lenalidomide and Azacitidine
Female	13
Male	24

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Lenalidomide and Azacitidine
Hispanic or Latino	2
Not Hispanic or Latino	28
Unknown or Not Reported	7

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Lenalidomide and Azacitidine
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	36
More than one race	0
Unknown or Not Reported	0

Region of Enrollment
Region of Enrollment(participants)	Lenalidomide and Azacitidine
United States	37

Study locations

3 sites

University of California at Los Angeles
Los Angeles, California 90095-1781, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida 33612-9497, United States
Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center
Cleveland, Ohio 44195, United States

References and documents

Publications

Sekeres MA, Tiu RV, Komrokji R, Lancet J, Advani AS, Afable M, Englehaupt R, Juersivich J, Cuthbertson D, Paleveda J, Tabarroki A, Visconte V, Makishima H, Jerez A, Paquette R, List AF, Maciejewski JP. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood. 2012 Dec 13;120(25):4945-51. doi: 10.1182/blood-2012-06-434639. Epub 2012 Aug 22. PubMed 22915641 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 19, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00352001
Lead sponsor: Mikkael Sekeres MD
Collaborators: National Cancer Institute (NCI)
Responsible party: Mikkael Sekeres MD (Principal Investigator, Case Comprehensive Cancer Center) — Sponsor-investigator
First posted: Jul 14, 2006
Start date: May 2006
Primary completion: Sep 2011
Completion: Sep 2011
Results posted: Sep 19, 2018
Last update: Sep 19, 2018

Study contacts

Mikkael A. Sekeres, MD, MS

study chair · The Cleveland Clinic

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2018. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Preleukemia→

Start the discussion