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


Phase 1
18 Years
64 Years
Open (Enrolling)
Both
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(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Recurrent Adult Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia

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Trial Information

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


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
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.


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 AML are eligible

- No granulocytic sarcoma as the sole site of disease

- No advanced malignant solid tumors or additional active hematologic malignancies

- No active central nervous system (CNS) disease

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

- 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 > 50 mL/min

- Left ventricular ejection fraction (LVEF) ≥ 40%

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception (one highly effective
method and one additional effective method) for ≥ 28 days before, during, and for ≥
28 days after completion of study treatment

- Patients with active infection are eligible provided the infection is under control

- Patients with uncontrolled infection may be enrolled after the infection is
treated and brought under control

- Patients with a comorbid medical illness are eligible provided their life expectancy
attributed to the illness is > 6 months

- No comorbidities that would preclude safety evaluation of study treatment

- No uncontrolled concurrent illness including, but not limited to, any of the
following:

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Serious cardiac arrhythmia

- Psychiatric illness or social situations that would limit compliance with study
requirements

- Myocardial infarction within the past 6 months

- NYHA class III-IV heart failure

- Severe uncontrolled ventricular arrhythmias

- Electrocardiographic evidence of acute ischemia or active conduction system
abnormalities

- No serious medical or psychiatric illness that would interfere with study
participation

- No known HIV positivity

- No history of medically serious allergic reactions or non-hematologic toxicities
attributed to the agents in this study 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

- No history of neurologic toxicity with cytarabine

- Prior lenalidomide, cytarabine, and/or idarubicin allowed provided that the
combination of the 3 agents has never before been administered and that no
lenalidomide has been administered for ≥ 6 months

- Recovered from the adverse events due to agents administered > 4 weeks ago

- More than 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy

- At least 14 days since prior and no other concurrent investigational agents

- No concurrent palliative radiotherapy

- No other concurrent commercial agents or therapies administered with the intent to
treat the patient's leukemia

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

William Blum

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-01375

NCT ID:

NCT01132586

Start Date:

May 2010

Completion Date:

Related Keywords:

  • 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(15;17)(q22;q12)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Recurrent Adult Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Ohio State University Medical CenterColumbus, Ohio  43210