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Phase II Trial of Lenalidomide in Older Patients (>/= 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities

Phase 2
60 Years
Not Enrolling
Leukemia, Myeloid, Acute

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Trial Information

Phase II Trial of Lenalidomide in Older Patients (>/= 60 Years) With Untreated Acute Myeloid Leukemia Without Chromosome 5q Abnormalities

The incidence of AML increases with age, and current treatment options for the older patient
population with newly diagnosed AML (AML >= 60) is limited, all with poor outcomes. AML >=
60 patients are more likely to have poor-risk cytogenetics abnormalities, and many have a
preceding myelodysplastic syndrome (MDS). Traditional induction chemotherapy approaches in
AML with cytarabine and anthracyclines yield remissions in 45-60% of AML >= 60, however the
vast majority of these patients relapse with a median survival of about 9 months. These
patients are rarely candidates for potentially curative allogeneic stem cell
transplantation. Many untreated AML >= 60 patients are not candidates for aggressive
therapy, and those who do receive therapy have a significant induction mortality of 10-20%,
and significant hematologic toxicity occurs in over 30%, with no change in overall survival
compared with supportive care. AML >= 60 patients with favorable risk cytogenetics have a
modest improvement in prognosis, for example with a 5 year overall survival of ~20%,
compared with 0% in other cytogenetic categories. Thus, all eligible patients with AML >=
60 should be recommended a clinical trial, regardless of whether they would be offered
generally ineffective traditional induction chemotherapy. More effective and less toxic
therapies are needed for the treatment of AML in this older patient population, indeed the
preferred first line therapy in the national cancer center network (NCCN) guidelines for AML
is a clinical trial.

In trials of lenalidomide in patients with MDS the dose of lenalidomide has been reduced for
myelotoxicity and/or thrombocytopenia. However, current paradigms for the therapy of acute
myeloid leukemia are based on using high doses of myelosuppressive chemotherapy and
supporting the patient through a 4-5 weeks period of neutropenia/thrombocytopenia in an
attempt to eliminate the malignant clone. Based on its efficacy in the related myeloid
disorder MDS, and the close relationship between MDS and AML in patients > 60, this trial
employs the same paradigm of myelosuppressive therapy using high dose lenalidomide instead
of chemotherapy. Importantly, within the MDS trials using low doses of lenalidomide,
responses were observed in 3/9 (33%) of patients with excess blasts (RAEB/RAEB-t), which are
now classified as evolving into AML or AML. This suggests that the therapeutic effect of
lenalidomide occurs in the setting of a large percentage of blasts, such as AML, although
the dose and schedule of lenalidomide administration is different. The response of AML >=
60 patients to the proposed high dose lenalidomide regimen is unknown. Following high dose
lenalidomide, in those patients that have a response, we propose using a lower dose
maintenance strategy similar to the FDA approved dosing for MDS. The maintenance phase will
include standard dose reductions for unacceptable toxicities.

Inclusion Criteria:

- AML, de novo, secondary to prior therapy, or transformed from MDS, as defined by the
International Working Group (except acute promyelocytic leukemia (AML M3). Patients
must not have abnormalities of chromosome 5q as assessed by routine cytogenetics or
FISH. Diagnosis of AML by WHO criteria (≥20% blasts) is determined by CBC, bone
marrow assessment, and immunophenotypic analysis performed within 2 weeks of study

- Intermediate or poor-risk cytogenetics as defined by SWOG criteria

- Age ≥ 60 years at the time of signing the informed consent form.

- Understand and voluntarily sign an informed consent form.

- Able to adhere to the study visit schedule and other protocol requirements.

- No previous treatment for AML, however hydroxyurea, steroids, and leukopheresis are

- ECOG performance status of ≤ 2 at study entry.

- Life expectancy > 2 months

- Adequate organ function as defined by:

- Serum creatinine ≤ 1.5X institution upper limit of normal (ULN)

- Total bilirubin ≤ 2.0 mg/dL

- AST (SGOT) and ALT (SGPT) ≤ 5 x ULN

- 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 prior to
and again within 24 hours of starting 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. All
patients must be counseled at a minimum of every 28 days about pregnancy precautions
and risks of fetal exposure.

- Disease free of prior malignancies for ≥ 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
or breast.

Exclusion Criteria:

- Received prior treatment for AML

- Favorable risk cytogenetic abnormalities as defined by SWOG criteria
( that include:
inv(16)/t(16;16)/del(16q), t(15;17) with/without secondary aberrations, t(8;21)
lacking del(9q) or complex karyotype (16). Prior to enrollment, FISH, molecular
studies or routine cytogenetics must be completed to rule out these cytogenetic

- Known CNS leukemia

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.

- Any condition, including the presence of laboratory abnormalities, which 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.

- Use of any other experimental drug or therapy within 30 days of enrollment.

- Known hypersensitivity to thalidomide.

Type of Study:


Study Design:

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

Outcome Measure:

To assess the morphologic complete remission rate (CR) of lenalidomide therapy in this patient population

Outcome Time Frame:

30 days, 60 days, and after 2 cycles of low dose therapy

Safety Issue:


Principal Investigator

Ravi Vij, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University in St. Louis


United States: Food and Drug Administration

Study ID:




Start Date:

February 2007

Completion Date:

March 2012

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Washington University School of MedicineSaint Louis, Missouri  63110