Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

Related Clinical Trial
A Study of CG-806 in Patients With Relapsed or Refractory Acute Myeloid Leukemia Total Marrow Irradiation for Refractory Acute Leukemia Phase I Combination of Midostaurin, Bortezomib, and Chemo in Relapsed/Refractory Acute Myeloid Leukemia Therapeutic Allogeneic Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Organ-Sparing Marrow-Targeted Irradiation Before Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS) Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission 3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia PXD101 in Treating Patients With Acute Myeloid Leukemia Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Bendamustine and Idarubicin in Treating Older Patients With Previously Untreated AML or MDS Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome SJG-136 in Treating Patients With Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndromes, Blastic Phase Chronic Myelogenous Leukemia, or Chronic Lymphocytic Leukemia Daunorubicin Hydrochloride, Cytarabine and Oblimersen Sodium in Treating Patients With Previously Untreated Acute Myeloid Leukemia GTI-2040 and High-Dose Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia Connect® MDS/AML Disease Registry Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia Vorinostat in Treating Patients With Acute Myeloid Leukemia Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia Economic Analysis of Blood Product Transfusions According to the Treatment of Acute Myeloid Leukaemia in the Elderly Comparison of Diagnostic Yield Among M-FISH, FISH Probe Panel and Conventional Cytogenetic Analysis in AML Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia Bortezomib in Treating Young Patients With Refractory or Recurrent Leukemia Red Cell Transfusion Goals in Patients With Acute Leukemias A PALG Prospective Multicenter Clinical Trial to Compare the Efficacy of Two Standard Induction Therapies (DA-90 vs DAC) and Two Standard Salvage Regimens (FLAG-IDA vs CLAG-M) in AML Patients ≤ 60 Years Old An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia Fludarabine and Cytarabine as Continuous Infusion Plus G-CSF Priming for Elderly Patients With Resistant AML Phase I/II Trial of ATRA and TCP in Patients With Relapsed or Refractory AML and no Intensive Treatment is Possible Prognostic Values of Next Generation Sequencing (NGS) in Acute Myeloid Leukemia Patients With Allo-HSCT PET/MRI, 18F-FDG PET/CT and Whole Body MRI in Finding Extramedullary Myeloid Leukemia in Patients With Newly Diagnosed Acute Myeloid Leukemia Pilot Clinical Trial of Pazopanib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or at Initial Diagnosis When no Intensive Treatment is Possible A Safety Study of SGN-CD33A in AML Patients FLAG+Ida With G-CSF Priming for Patients Younger Than 60 Years With Resistant AML Study on Number and Outcome of Pregnancy in Acute Promielocitic Leukaemia (APL) Patients Treated With Chemotherapy Biomarkers in Bone Marrow Samples From Patients With Acute Promyelocytic Leukemia Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia A Study for Improving the Outcome of Childhood Acute Promyeloid Leukemia ASCT for Relapsed APL After Molecular Remission Diagnostic Study of Patients With Acute Lymphoblastic Leukemia or Acute Promyelocytic Leukemia National Acute Promyelocytic Leukemia (APL) Observational Study NAPOLEON-Registry of the German AML Intergroup All-trans Retinoic Acid, and Arsenic +/- Idarubicin Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL Randomized,International Multi-center Clinical Trial of RIF Plus RA for Non-high-risk APL Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia AIDA 2000 Guidelines Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia The Acute Promyelocytic Leukaemia Asian Consortium (APL-AC) Project Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL French Registry of First-line Treatment of Acute Promyelocytic Leukemia New Retinoid Agent Combined With Arsenic Trioxide for Untreated Acute Promyelocytic Leukemia Combined Tretinoin and Arsenic Trioxide for Patients With Newly Diagnosed Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Promyelocytic Leukemia Treatment of Relapsed Promyelocytic Leukemia With Arsenic Trioxide (ATO) Treatment of Newly Diagnosed Patients With Acute Promyelocytic Leukemia (PETHEMA LPA 2005) Long-Term Quality of Life in Patients With Acute Promyelocytic Leukemia Tamibarotene and Arsenic Trioxide for Relapsed Acute Promyelocytic Leukemia Long-term QoL in Acute Promyelocytic Leukemia Treated With ATO or Standard Chemotherapy Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF) Treatment of Acute Promyelocytic Leukemia With All-Trans Retinoic Acid (ATRA) and Idarubicin (AIDA) Single Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia Study for Patients With Newly Diagnosed, High-risk Acute Promyelocytic Leukemia Treatment Protocol for Relapsed Acute Promyelocytic Leukemia (APL) With Arsenic Study of NRX 195183 Therapy for Patients With Relapsed or Refractory Acute Promyelocytic Leukemia Oral Arsenic Trioxide for Newly Diagnosed Acute Promyelocytic Leukaemia Role of Microparticles in the Coagulopathy of Acute Promyelocytic Leukemia Proteasome Inhibition in Acute Promyelocytic Leukemia

Brief Title

Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

Official Title

Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia

Brief Summary

      This phase I trial studies the side effects and best dose of lenalidomide when given together
      with cytarabine and idarubicin in treating patients with acute myeloid leukemia. Biological
      therapies, such as lenalidomide, may stimulate the immune system in different ways and stop
      cancer cells from growing. Drugs used in chemotherapy, such as cytarabine and idarubicin,
      work in different ways to stop the growth of cancer cells, either by killing the cells or by
      stopping them from dividing. Giving lenalidomide together with cytarabine and idarubicin may
      kill more cancer cells.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with
      conventional chemotherapy in two separate cohorts of patients with 1) relapsed or refractory
      acute myeloid leukemia (AML) and 2) age >= 60 with untreated AML and recommend starting doses
      for phase II studies of this combination of agents.

      SECONDARY OBJECTIVES:

      I. To define the qualitative and quantitative toxicities of these combinations of agents in
      regard to organ specificity, time course, predictability, and reversibility.

      II. To document the therapeutic response of these combinations of agents in patients with
      poor risk AML.

      III. To conduct pharmacodynamic studies to investigate the potential mechanism of
      lenalidomide activity in this trial.

      OUTLINE: This is a dose-escalation study of lenalidomide.

      INDUCTION:

      COHORT I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, cytarabine
      intravenously (IV) continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on
      days 5-7.

      COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over
      24 hours on days 5-11, and idarubicin as above.

      Patients with residual disease on day 18 undergo a second course of induction therapy.

      CONSOLIDATION:

      COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days
      5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence
      of disease progression or unacceptable toxicity.

      COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO
      QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every
      28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 30 days.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

MTD of lenalidomide, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Secondary Outcome

 Qualitative and quantitative toxicities, graded using NCI CTCAE version 4.0

Condition

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Intervention

Lenalidomide

Study Arms / Comparison Groups

 Treatment (lenalidomide, cytarabine, idarubicin)
Description:  INDUCTION:
COHORT I: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.
COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.
Patients with residual disease on day 18 undergo a second course of induction therapy.
CONSOLIDATION:
COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

61

Start Date

May 2010

Completion Date

January 2014

Primary Completion Date

January 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Cohort 1: Patients must be age >= 18 and < 65 with relapsed or refractory AML or high
             risk myelodysplastic syndrome (MDS); high risk MDS is defined as international
             prognosis scoring system (IPSS) score of 1.5 or higher; eligible patients will have a
             score of 1.5 or higher at any time from diagnosis to screening

               -  Cohort 2: Patients must be age >= 18 with previously untreated AML; favorable
                  risk AML patients < 60 years of age are excluded; these are defined as core
                  binding factor (CBF) AML patients and characterized by cytogenetic or molecular
                  evidence of CBF leukemia; untreated AML patients < 60 years of age must be
                  negative on screening for CBF leukemia by cytogenetic or molecular analysis
                  (Note: Prior therapy for MDS is permitted)

          -  Patients with secondary AML or therapy-related disease (transformed [t]-AML/MDS) are
             eligible

          -  If the patient has co-morbid medical illness, life expectancy attributed to this must
             be greater than 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Total bilirubin < 2.0 mg/dL

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper
             limit of normal

          -  Creatinine < 2.0 mg/dL AND creatinine clearance (calculated) >= 50 mL/min

          -  Left ventricular ejection fraction (LVEF) >= 40%

          -  Patients who have previously received lenalidomide, idarubicin, and/or cytarabine are
             eligible provided that the combination of the 3 agents has never before been
             administered, and that no lenalidomide has been administered for at least 6 months

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a minimum sensitivity of at least 25 mIU/mL within 10-14 days prior to and
             again within 24 hours of starting lenalidomide and must either commit to continued
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control, one highly effective method and one additional effective method AT THE SAME
             TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to
             ongoing pregnancy testing; men must agree to use a latex condom during sexual contact
             with a FCBP even if they have had a successful vasectomy; these methods of birth
             control must be used for the duration of study participation and for 28 days after
             lenalidomide discontinuation; all patients must be counseled at a minimum of every 28
             days about pregnancy precautions and risks of fetal exposure

          -  Ability to understand and willingness to sign the written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study, or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients who have taken lenalidomide within the last 6 months

          -  Patients receiving any other investigational agents or patients that have received
             other investigational agents within 14 days of enrollment

          -  Patients with active central nervous system disease or with granulocytic sarcoma as
             sole site of disease

          -  Patients with history of medically serious allergic reactions or non-hematologic
             toxicities attributed to the agents in this trial such as lenalidomide or thalidomide
             or compounds of similar chemical or biologic composition that are not easily managed,
             or patients with a history of cerebellar toxicity to cytarabine

          -  Patients with the following will be excluded: uncontrolled intercurrent illness
             including, but not limited to, symptomatic congestive heart failure, unstable angina
             pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that
             would limit compliance with study requirements, myocardial infarction within 6 months
             prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure,
             severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities; patients with medical
             comorbidities that will preclude safety evaluation of the combination should not be
             enrolled

          -  Patients with serious medical or psychiatric illness likely to interfere with
             participation in this clinical study

          -  Pregnant women or women who are breastfeeding; additional pregnancy testing before,
             during, and after lenalidomide treatment is required, as well as requirements for
             contraception before, during, and after lenalidomide treatment

          -  Patients with advanced malignant solid tumors are excluded; patients with active
             additional hematologic malignancies are excluded

          -  Patients with a history of neurologic toxicity with cytarabine are excluded

          -  As infection is a common feature of AML, patients with active infection are permitted
             to enroll provided that the infection is under control; patients with uncontrolled
             infection shall not be enrolled until infection is treated and brought under control

          -  Known human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate
             studies will be undertaken in HIV + patients once safety of the combination has been
             demonstrated
      

Gender

All

Ages

18 Years - 64 Years

Accepts Healthy Volunteers

No

Contacts

William Blum, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01132586

Organization ID

NCI-2011-01375

Secondary IDs

NCI-2011-01375

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

William Blum, Principal Investigator, Ohio State University Comprehensive Cancer Center


Verification Date

November 2014