Idarubicin + Cytarabine and Lenalidomide in Patients With Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML)
A Phase 1/2 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients With Myelodysplastic Syndrome (RAEB-2) or With Previously Untreated Acute Myeloid Leukemia
2 other identifiers
interventional
51
1 country
2
Brief Summary
The purpose of this study is to:
- Test the safety of the research study drug, lenalidomide, when given with Idarubicin and Cytarabine
- See how many respond to combination treatment with lenalidomide, Idarubicin and Cytarabine
- See how long people respond to this combination therapy
- See how long people live after being treated with this combination of drugs
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2009
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2009
CompletedFirst Posted
Study publicly available on registry
January 29, 2009
CompletedStudy Start
First participant enrolled
June 25, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 17, 2015
CompletedResults Posted
Study results publicly available
March 28, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 16, 2020
CompletedDecember 22, 2020
December 1, 2020
5.7 years
January 28, 2009
February 25, 2016
December 1, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase I: Recommended Phase II Dose
For the Phase I component, no formal statistical analysis was planned. The primary endpoint is to determine the maximum tolerated dose (MTD) and recommended Phase II dose of lenalidomide given in combination with standard idarubicin + cytarabine induction therapy.
18 months
Phase II: Complete Response Rate of Participants Treated at Maximum Tolerated Dose (MTD)
Percentage of participants achieving CR/CRi. Complete Response (CR) plus Complete Response with Incomplete Count Recovery (CRi) rates. Response rates (CR + CRi) of lenalidomide following idarubicin and cytarabine induction therapy in older patients with previously untreated AML. A CR designation requires that the patient achieve the morphologic leukemia-free state and have an absolute neutrophil count of more than 1,000/μL and platelets of 100,000/μL. CRi: After chemotherapy, patients fulfill all of the criteria for CR except for residual neutropenia (1,000/μL) or thrombocytopenia (100,000/μL).
24 months
Secondary Outcomes (3)
Rate of Lenalidomide Related Toxicity During Maintenance Therapy
24 months
Median Progression-Free Survival (PFS)
24 months
Median Overall Survival (OS)
Up to 24 Months
Other Outcomes (2)
Rate of Cytogenetic Remission Following Induction Therapy
24 Months
Median Relapse-Free Survival (RFS)
24 Months
Study Arms (2)
Phase I: Dose Escalation
EXPERIMENTALInduction: A dose escalation plan for induction therapy using a standard 3x3 design with dose escalation of Lenalidomide only, to determine maximum tolerated dose (MTD). Idarubicin and cytarabine doses will be fixed. Idarubicin: 12 mg/m\^2. Cytarabine: 200 mg/m\^2. Lenalidomide: According to dose escalation levels. Level 1: 5 mg/d; Level 2: 10 mg/d; Level 3: 15 mg/d; Level 4: 20 mg/d; Level 5: 25 mg/d.
Phase II: Treatment at MTD
EXPERIMENTALIdarubicin: 12 mg/m\^2. Cytarabine: 200 mg/m\^2. Lenalidomide: Maximum Tolerated Dose (MTD).
Interventions
Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms.
Intravenous infusion of Idarubicin as outlined in Phase I and Phase II Treatment Arms.
Lenalidomide as outlined in Phase I and Phase II Treatment Arms.
Eligibility Criteria
You may qualify if:
- Understand and voluntarily sign an informed consent form
- Able to adhere to the study visit schedule and other protocol requirements
- Disease-specific criteria (Phase I):
- Previously untreated Acute Myeloid Leukemia (AML), associated with monosomy 5 or segmental deletion involving 5q31, either alone or with additional cytogenetic abnormalities
- Previously untreated AML (age ≥ 60 years)
- Myelodysplastic Syndrome, Refractory Anemia with Excess Blasts-2 (MDS,RAEB-2, 10-19% blasts in the bone marrow) associated with monosomy 5 or segmental deletion involving 5q31, either alone or with additional cytogenetic abnormalities
- For MDS, patients must have had progression with or failed response to front-line therapy with a nucleoside analogue (azacitidine, decitabine).
- Disease Specific Criteria (Phase II)
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry
- Left ventricular ejection fraction (LVEF) ≥ 50%
- Laboratory test results within these ranges:
- Serum creatinine ≤ 2.0 mg/dL
- Total bilirubin ≤ 1.5 mg/dL (Gilbert's syndrome excluded)
- Aspartic transaminase (AST) and Alanine transaminase (ALT) ≤ 2 x upper limit of normal (ULN)
- Disease free of prior malignancies for ≥ 2 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast
- +6 more criteria
You may not qualify if:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- Unwilling or unable to participate with Food and Drug Administration (FDA) mandated birth control and pregnancy guidelines
- Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Use of any other experimental drug or therapy within 28 days of baseline
- Known hypersensitivity to thalidomide
- The development of erythema nodosum, if characterized by a desquamating rash, while taking thalidomide or similar drugs
- Any prior use of lenalidomide
- AML with cytogenetics including t(15;17), t(8;21), or inv(16)
- White blood count (WBC) count ≥ 50,000 on hydroxyurea therapy
- Previous history of induction chemotherapy for AML or allogeneic stem cell transplant
- Predicted inability to tolerate standard induction chemotherapy with idarubicin and cytarabine
- History of spontaneous thromboembolic event requiring use of anticoagulation with warfarin (coumadin) or low molecular-weight heparin within 3 years
- Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- H. Lee Moffitt Cancer Center and Research Institutelead
- Celgenecollaborator
Study Sites (2)
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, 44195, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Jeffrey Lancet
- Organization
- H. Lee Moffitt Cancer Center and Research Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Jeffrey Lancet, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2009
First Posted
January 29, 2009
Study Start
June 25, 2009
Primary Completion
February 17, 2015
Study Completion
November 16, 2020
Last Updated
December 22, 2020
Results First Posted
March 28, 2016
Record last verified: 2020-12