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

October 25, 2018 updated by: David Iberri, Stanford University

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University, School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (lenalidomide, combination chemotherapy)

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.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cytarabine
Given IV
Other Names:
  • Cytosar-U
  • cytosine arabinoside
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
Drug: mitoxantrone hydrochloride
Given IV
Other Names:
  • CL 232315
  • DHAD
  • DHAQ
  • Novantrone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 42 days
Hematologic and non-hematologic toxicities will be tabulated.
42 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate (complete remission [CR], CR with incomplete blood count recovery [CRi], partial remission [PR] or stable disease [SD]) using LeukemiaNet guidelines
Time Frame: Up to 6 months
Proportions of these patients in each response category will be tabulated; the combined proportion in categories CR, CRi, PR, and SD will be computed along with an exact 95% confidence interval.
Up to 6 months
Response duration
Time Frame: From start of induction, assessed up to 6 months
Summarized using a Kaplan-Meier plot.
From start of induction, assessed up to 6 months
Early mortality
Time Frame: From start of induction, assessed up to 6 months
Summarized using a Kaplan-Meier plot.
From start of induction, assessed up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: David Iberri, Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (ACTUAL)

May 13, 2015

Study Completion (ACTUAL)

July 18, 2015

Study Registration Dates

First Submitted

July 17, 2013

First Submitted That Met QC Criteria

July 17, 2013

First Posted (ESTIMATE)

July 22, 2013

Study Record Updates

Last Update Posted (ACTUAL)

October 29, 2018

Last Update Submitted That Met QC Criteria

October 25, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-27313 (OTHER: Stanford IRB)
  • P30CA124435 (U.S. NIH Grant/Contract)
  • NCI-2013-01349 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • HEMAML0024 (OTHER: OnCore ID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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