Mitoxantrone, Etoposide, Cytarabine, and Lenalidomide in Treating Patients with Relapsed or Refractory Acute Myeloid Leukemia

Status: Active

Description

This phase II trial studies how well mitoxantrone, etoposide, cytarabine, and lenalidomide work in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Drugs used in chemotherapy, such as mitoxantrone, etoposide, cytarabine, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Eligibility Criteria

Inclusion Criteria

  • Acute myelogenous leukemia diagnosed by World Health Organization (WHO) criteria with one of the following (patients with biphenotypic leukemia are eligible, provided that the treating physician determines an acute myeloid leukemia [AML] treatment regimen is appropriate) * Primary refractory disease following >= 1 cycle of induction chemotherapy * First relapse or higher; patients with primary or secondary acute myelogenous leukemia are eligible
  • Left ventricular ejection fraction (LVEF) >= 50 %
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Able to adhere to study schedule and other protocol requirements
  • Unless felt due to underlying disease and approved by the overall principal investigator (PI): Creatinine < 2.0 mg/dl, and estimated glomerular filtration rate (eGFR) >= 60 mL/min (within 21 days of the start of treatment)
  • Unless felt due to underlying disease and approved by the overall PI: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN); patients with Gilbert’s disease may have total bilirubin up to =< 3 x institutional ULN (within 21 days of the start of treatment)
  • Unless felt due to underlying disease and approved by the overall PI: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN (within 21 days of the start of treatment)
  • Patients may receive hydroxyurea, steroids, or leukapheresis as necessary until day 5 of treatment
  • Patients must give voluntary written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Patients may have had prior treatment for myelodysplastic syndrome (MDS) or AML, including prior lenalidomide for MDS or AML or another condition
  • Patient may have had prior autologous or allogeneic transplant (family member, unrelated donor, or cord blood) if there is at least 90 days between transplant and study entry
  • Patients may also have had donor lymphocyte infusion if there is at least 60 days between donor lymphocyte infusion and study entry
  • Patients on immunosuppression are also eligible
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL prior to receiving treatment with 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 * A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Ability to understand and the willingness to sign a written informed consent document
  • All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program, and be willing and able to comply with the requirements of the REMs program; females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program

Exclusion Criteria

  • Known hypersensitivity to thalidomide or lenalidomide (if applicable)
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Known seropositive for human immunodeficiency virus (HIV); HIV testing is not required; hepatitis testing is not required
  • Patients who have had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Any serious medical condition laboratory abnormality or psychiatric illness that would prevent the subject from signing the consent form
  • Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Patients with major surgery within 28 days prior to treatment
  • Patients with any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol
  • Patient has received an investigational agent or cytotoxic chemotherapy (excluding hydroxyurea) within 7 days of study entry; if an LP is performed for clinical care, intrathecal chemotherapy (although not systemic chemotherapy) may be given as prophylaxis per institutional standard of care, but should be completed > 24 hours prior to administration of protocol therapy
  • Patients with acute promyelocytic leukemia
  • Females who are pregnant

Locations & Contacts

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Active
Contact: Lourdes M. Mendez
Phone: 617-667-9920
Email: lmendez@bidmc.harvard.edu
Brigham and Women's Hospital
Status: Active
Contact: Richard M. Stone
Phone: 617-632-2214
Email: RSTONE@PARTNERS.ORG
Dana-Farber Cancer Institute
Status: Active
Contact: Richard M. Stone
Phone: 617-632-2214
Email: RSTONE@PARTNERS.ORG
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Andrew Mark Brunner
Phone: 617-724-1124
Email: abrunner@partners.org

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Contact: Michael Kenneth Keng
Phone: 434-924-4257
Email: Mk2pv@hscmail.mcc.virginia.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To assess rates of complete remission (CR) and rates of complete remission with incomplete platelet recovery (CRp) after treatment with mitoxantrone, etoposide, cytarabine (MEC) and lenalidomide.

SECONDARY OBJECTIVES:

I. To evaluate the days to neutrophil recovery (the first of 3 days of absolute neutrophil count [ANC] > 500).

II. To evaluate the days to platelet recovery (platelet count > 20K unsupported).

III. To evaluate the treatment-related mortality (the number of non-relapse related deaths in the first 50 days of starting treatment).

IV. To evaluate the transfusion support (the number of red blood cell and platelet transfusions needed in the first 50 days of treatment).

V. To determine if certain genetic profiles of the leukemia predict for better response (optional correlate).

OUTLINE:

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-10, mitoxantrone intravenously (IV) over 6-10 minutes on days 4-8, etoposide IV over 1 hour on days 4-8, and cytarabine IV over 1 hour on days 4-8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients for followed for 50 days, at 3 months, and then every 6 months for up to 3 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Andrew Mark Brunner

Trial IDs

Primary ID 16-574
Secondary IDs NCI-2017-01703
Clinicaltrials.gov ID NCT03118466