Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Brief Title

Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

A Phase I Study of Lenalidomide Therapy Prior to Re-induction Chemotherapy With Mitoxantrone, Etoposide, and Cytarabine (MEC) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML)

Brief Summary

      This phase I trial studies the side effects and the best dose of lenalidomide when given
      together with combination chemotherapy in treating patients with relapsed or refractory acute
      myeloid leukemia. Lenalidomide may stop the growth of acute myeloid leukemia by blocking
      blood flow to the cancer. Drugs used in chemotherapy, such as mitoxantrone hydrochloride,
      etoposide, and cytarabine, work in different ways to stop the growth of cancer cells, either
      by killing the cells or by stopping them from dividing. Giving lenalidomide and combination
      chemotherapy may be an effective treatment for acute myeloid leukemia.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) of lenalidomide when used in combination
      with mitoxantrone hydrochloride, etoposide, and cytarabine (MEC) in patients with relapsed or
      refractory acute myeloid leukemia (AML).

      II. To determine the dose-limiting toxicities (DLTs) of this combination in this patient
      population.

      SECONDARY OBJECTIVES:

      I. To determine whether the combination of lenalidomide priming prior to re-induction
      chemotherapy with MEC has clinical activity in patients with relapsed or refractory AML.

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

      LENALIDOMIDE PRIMING: Patients receive lenalidomide orally (PO) for 5 or 7 days.

      RE-INDUCTION CHEMOTHERAPY: Patients receive etoposide intravenously (IV) over 1 hour,
      cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-5.
      Patients failing to achieve blast count < 5% at 21 days may receive a second course of
      induction therapy. Patients achieving complete remission proceed to lenalidomide priming.

      LENALIDOMIDE PRIMING: Within 4-6 weeks, patients receive lenalidomide PO for 5 or 7 days and
      then proceed to consolidation therapy.

      CONSOLIDATION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3
      hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-4. Treatment repeats
      every 28-35 days for up to 2 courses in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 6 months.
    

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

MTD of lenalidomide when used in combination with MEC determined by DLT using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

Secondary Outcome

 Response rate (complete remission [CR], CR with incomplete blood count recovery [CRi], partial remission [PR] or stable disease [SD]) using LeukemiaNet guidelines

Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

lenalidomide

Study Arms / Comparison Groups

 Treatment (lenalidomide, combination chemotherapy)

Description:  LENALIDOMIDE PRIMING: Patients receive lenalidomide PO for 5 or 7 days.
RE-INDUCTION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-5. Patients failing to achieve blast count < 5% at 21 days may receive a second course of induction therapy. Patients achieving complete remission proceed to lenalidomide priming.
LENALIDOMIDE PRIMING: Within 4-6 weeks, patients receive lenalidomide PO for 5 or 7 days and then proceed to consolidation therapy.
CONSOLIDATION CHEMOTHERAPY: Patients receive etoposide IV over 1 hour, cytarabine IV over 3 hours, and mitoxantrone hydrochloride IV over 15-30 minutes on days 1-4. Treatment repeats every 28-35 days for up to 2 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 Status

Drug

Estimated Enrollment

17

Start Date

February 2014

Completion Date

July 18, 2015

Primary Completion Date

May 13, 2015

Eligibility Criteria

        Inclusion Criteria:

          -  Patients eligible include those with diagnosis of AML other than acute promyelocytic
             leukemia by World Health Organization (WHO) criteria with relapsed disease after
             induction therapy or refractory to induction chemotherapy, as determined by morphology
             on bone marrow biopsy; also eligible are patients unwilling to receive standard
             induction chemotherapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Serum creatinine =< 1.5 mg/dL; if serum creatinine > 1.5 mg/dL, then the estimated
             glomerular filtrate rate (GFR) must be > 60ml/min/1.73m^2 as calculated by the
             Modification of Diet in Renal Disease equation

          -  Serum bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is considered to
             be secondary to Gilbert's syndrome, hemolysis, or hepatic infiltration by AML

          -  Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN

          -  Alkaline phosphatase =< 2.5 x ULN

          -  All study participants must be registered into the mandatory Revlimid assistance
             (RevAssist) program, and be willing and able to comply with the requirements of
             RevAssist

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24
             hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled
             within 7 days as required by RevAssist) 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

        Exclusion Criteria:

          -  Patient must not undergo concomitant radiotherapy, chemotherapy or immunotherapy;
             patient must not be in concurrent study with other investigational agents

          -  Patients who have received prior lenalidomide therapy are not eligible for this study;
             further there should be at least a 14-day window from the patient's last prior therapy
             before initiation of treatment on clinical trial

          -  Have other severe concurrent disease or serious organ dysfunction involving the heart,
             kidney, liver or other organ system that may place the patient at undue risk to
             undergo treatment

          -  Have significant, uncontrolled active infection

          -  Pregnant or nursing patients will be excluded from the study

          -  Known human immunodeficiency virus (HIV) infection
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

David Iberri, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01904643

Organization ID

IRB-27313

Secondary IDs

NCI-2013-01349

Responsible Party

Principal Investigator

Study Sponsor

Stanford University

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

David Iberri, Principal Investigator, Stanford University

Verification Date

October 2018