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LeukemiaPhase 1/2NCT00352001

Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

A Phase 1/2 study testing azacitidine and lenalidomide in people with Leukemia and Myelodysplastic Syndromes, run by Mikkael Sekeres MD at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Leukemia, Myelodysplastic Syndromes
What is being tested?
azacitidine and lenalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
3 sitesUnited States
Study dates
May 2006to Sep 2011
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Cleveland Clinic Taussig Cancer Instititute, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44195

  • University of California at Los Angeles

    Los Angeles, California, 90095-1781

  • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

    Tampa, Florida, 33612-9497

Other trials in United States

About this study

Official title: A Phase I/II Study of Revlimid (Lenalidomide) in Combination With Vidaza (Azacitidine) in Patients With Advanced Myelodysplastic Syndrome (MDS)

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.

Keywords
refractory anemia with excess blasts, previously treated myelodysplastic syndromes, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, secondary myelodysplastic syndromes
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • azacitidineDrug

    Also called Vidaza®

    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.

  • lenalidomideDrug

    Also called Revlimid®

    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.

Study groups in NCT00352001
Study groupRoleWhat they receive
Lenalidomide and AzacitidineExperimentalNot described
Receives: Drug: azacitidine; Drug: lenalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: After 1 courses (1 months)

  2. 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

    Measured: After 4 courses (4 months)

  3. 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

    Measured: After 7 courses (months)

  4. 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.

    Measured: After 1 courses (1 months)

Secondary outcomes (4)

  1. 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

    Measured: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

  2. Time to Relapse After Achieving Complete Response

    Measured: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

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

    Measured: After 7 months

  4. Overall Survival Among Patients With Complete Response

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

    Measured: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2006 (estimated)
  2. Study startMay 2006
  3. Primary completionSep 2011
  4. Study completionSep 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00352001
Sponsor's protocol ID
CASE17Z05
Other IDs
P30CA016042, UCLA-0511032-01, UCLA-RDN-5405, UCLA-05011032-01, CASE17Z05
Status last verified
Sep 2018
First submitted
13 Jul 2006
Last updated
19 Sep 2018
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing azacitidine and lenalidomide in people with Leukemia and Myelodysplastic Syndromes, run by Mikkael Sekeres MD at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PHASE I: Maximum Tolerated Dose of Azacitidine (time frame: After 1 courses (1 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00352001, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2018.

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