This research study is evaluating the safety and tolerability of the drug lenalidomide in
combination with and following mismatched related donor microtransplantation in high risk AML
patients in first remission. This study also aims to define the maximum tolerated dose (MTD)
of lenalidomide given in this setting.
Microtransplantation seeks to give the participant donor cells in hopes that those cells can
attack the underlying cancer. However, since the donor cells do not replace all of the host
cells, it can hopefully avoid many of the serious risks involved with standard transplant,
including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the
participant's normal body. Recent studies have suggested that lenalidomide can help aid donor
cells to attack cancer when given after a stem cell transplant. This trial is trying to see
if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part
The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been
approved for other uses such as in the treatment of other cancers including multiple myeloma
and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has
not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the
Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact
antitumor mechanism of action of lenalidomide is unknown.
After the screening procedures confirm that the participant is eligible to participate in the
research study. The participant will be given a study drug-dosing calendar.
The investigators are looking for the highest dose of the study drug that can be administered
safely without severe or unmanageable side effects in participants, not everyone who
participates in this research study will receive the same dose of the study drug. The dose
given will depend on the number of participants who have been enrolled in the study prior and
how well they have tolerated their doses. Participants will receive the following:
- Recipient Inclusion Criteria
- Adults, aged 18 through 75 years of age, with pathologically confirmed acute
myelogenous leukemia, in pathologically confirmed complete remission following
- AST, ALT and Alkaline Phosphatase <5x Upper Limit normal (ULN), direct bilirubin < 2.0
- Adequate renal function as defined by: calculated creatinine clearance ≥ 60 mL/min
(Cockcroft-Gault Formula) or serum Cr less than institution ULN (the elderly will
often have < 60 GFR)
- ECOG performance status 0-2.
- Have a diagnosis of high-risk AML as established by a poor-risk karyotype, adverse
risk by ELN criteria, a therapy-related AML, age ≥ 60 or with antecedent hematologic
- LVEF must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram
- Patients, or appropriate designee, must be able to provide informed consent.
- Must not have received systemic anti-neoplastic therapy, including radiotherapy within
14 days of study treatment.
- Female patients of childbearing age must have negative pregnancy test.
- Male subject agrees to use an acceptable method for contraception during the entire
study treatment period and through 6 months after the last dose of lenalidomide.
- All study participants must be registered into the mandatory Revlimid REMS® program,
and be willing and able to comply with the requirements of the REMS® program.
- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS® program. If needed, patients should be able to take
aspirin (81 or 325 mg) daily as prophylactic anticoagulation.
- Donor Inclusion Criteria
- Haploidentical 1st-degree relative as defined by 3/6 or 4/6 HLA-matched at HLA -A, -B,
or -DRB1 who is 18-70 years of age
- ECOG performance status 0 or 1
- Excellent health per conventional pre-donor history (medical and psychosocial
- No positive testing for viral infection (HbsAg, HIV, HCV)
- Donor ability to understand and provide informed consent
- Meets standard institutional criteria for GCSF mobilized PBSC donation
- Recipient Exclusion Criteria
- Diagnosis of acute promyelocytic leukemia
- Active refractory or relapsed acute leukemia
- Prior use of fludarabine, as this agent has been associated with higher subsequent
rates of graft versus host disease
- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 3 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer
in situ, and basal cell or squamous cell carcinoma of the skin.
- Uncontrolled intercurrent illness that would limit compliance with study requirements.
- HIV-positive individuals on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with study drug. In addition, these
individuals are at increased risk of lethal infections when treated with
- A diagnosis of active hepatitis B or C as defined by detectable viral load assays in
- Known hypersensitivity to thalidomide or lenalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while
- Significant cardiac disease as determined by the investigator including:
- Known or suspected cardiac amyloidosis
- Congestive heart failure of Class III or IV of the NYHA classification
- Uncontrolled angina, hypertension or arrhythmia
- Myocardial infarction in past 6 months
- Any uncontrolled or severe cardiovascular disease
- Prior cerebrovascular event with persistent neurologic deficit
- Medical conditions that, in the investigator's opinion, would impose excessive risk to
- Equal to or greater than grade 2 ataxia, cranial or peripheral neuropathy.
- Systemic infection requiring IV antibiotic therapy within 7 days preceding the first
dose of study drug, or other severe infection.
- Pregnant women are excluded from this study.