Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Information source: Stanford University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia
Intervention: lenalidomide (Drug); mitoxantrone hydrochloride (Drug); etoposide (Drug); cytarabine (Drug)
Phase: Phase 1
Status: Suspended
Sponsored by: Stanford University Official(s) and/or principal investigator(s): Bruno de Medeiros, Principal Investigator, Affiliation: Stanford University Hospitals and Clinics
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.
Clinical Details
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)
Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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 guidelinesResponse duration Early mortality
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Stanford University Hospitals and Clinics, Stanford, California 94305, United States
Additional Information
Starting date: February 2014
Last updated: August 12, 2015
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