Velcade and Lenalidomide in Patients With Relapsed AML and MDS After Allogeneic Stem Cell Transplantation
Velcade and Lenalidomide in Patients With Relapsed AML and MDS After Allogeneic Stem Cell Transplantation
This research study is evaluating drugs called bortezomib and lenalidomide as a possible
 treatment for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

 The purpose of this research study is to determine the safety and efficacy of the bortezomib
 and lenalidomide investigational combination. This drug combination has been used in the
 treatment of relapsed/refractory multiple myeloma and has been previously investigated in the
 treatment of MDS and AML, albeit at a lower dose of lenalidomide. In this research study, the
 investigators are looking for the highest dose of the combination that can be given safely
 and see how well it works as a combination for MDS and AML in individuals whose disease has
 relapsed after an SCT.
-  After the screening procedures confirm participation in the research study:

 -  The participant will be given a study drug-dosing calendar for each treatment cycle. The
 investigators are looking for the highest dose of the combination of study drugs that
 can be administered safely without severe or unmanageable side effects in participants
 that have, 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 the dose was tolerated.

 -  Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in
 dose level I with dose cohorts and rules for escalation and de-escalation.

 -  Each treatment cycle lasts 28 days (4 weeks). The first two cycles are called the
 induction cycles. If the participant respond to treatment during the first two cycles,
 they can continue on to the maintenance cycles.

 -  Lenalidomide

 -  Bortezomib:
Inclusion Criteria:

 -  Participants must meet the following criteria on screening examination to be eligible
 to participate in the study:

 -  A diagnosis of recurrent, persistent, or progressive acute myelogenous leukemia (AML),
 defined as >= 5% blasts in a patient with known prior history of AML, or recurrent,
 persistent, or progressive myelodysplastic syndrome (MDS) according to WHO criteria.

 -  Must have undergone an allogeneic SCT (regardless of stem cell source)

 -  Patients must be 18 years or older

 -  Able to adhere to study schedule and other protocol requirements

 -  Must be off all immunosuppressive medications (except prednisone) for at least 2 weeks
 prior to study entry.

 -  Must be on less than 21 mg of oral prednisone daily for GVHD

 -  ECOG performance status 0-2 (see Appendix 2)

 -  Participants must have the following organ function all within 21 days prior to
 enrollment

 -  Total bilirubin ≤ 2.0 mg/dl unless due to underlying conjugation disease such as
 Gilbert's

 -  ALT and AST ≤ 3X the upper limit of normal

 -  Creatinine < 2.0 mg/dl

 -  Patients may receive hydroxyurea or leukopheresis as necessary

 -  Patients must give voluntary written informed consent and HIPA authorization before
 performance of any study-related procedure not part of normal medical care with the
 understanding that consent maybe withdrawn by the subject at any time without
 prejudice to future medical care.

 -  All previous cancer therapy including donor lymphocyte infusions must have been
 discontinued at least 2 weeks prior to treatment in this study.

 -  All study participants must be registered in the RevREMS® program and be willing and
 able to comply with the requirements of REMS® program.

 -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
 required in the Revlimid REMS® program.

 Exclusion Criteria:

 -  Participants who exhibit any of the following conditions at screening will not be
 eligible for admission into the study.

 -  Ejection fraction < 40% obtained by either MUGA or echocardiogram

 -  Patients who had had a myocardial infarction within 6 months of enrollment or have New
 York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina,
 uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
 ischemia or active conduction system abnormalities. Prior to study entry, any ECG
 abnormality at screening has to be documented by the investigator as not medically
 relevant.

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

 -  Any condition, including laboratory abnormalities, that in the opinion of the
 investigator places the subject at an unacceptable risk if he/she were to participate
 in the study or confounds the ability to interpret data from the study.

 -  Patients with major surgery within 28 days prior to trial enrollment

 -  Patients with greater than or equal to grade 2 peripheral neuropathy or active herpes
 infection

 -  Patients with ≥ grade 3 acute graft-versus-host disease are excluded from the study

 -  Patients with moderate or severe chronic graft-versus host requiring more than 20 mg
 of oral prednisone therapy are excluded from the study.

 -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
 or active infection, cirrhosis, chronic obstructive or restrictive pulmonary disease,
 symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

 -  Patients with any serious or medical or psychiatric illness that could, in the
 investigator's opinion, potentially interfere with the completion of treatment
 according to this protocol

 -  Female subject is pregnant or breast-feeding. Lactating females must agree not to
 breastfeed while taking lenalidomide.

 -  Patient has received an investigational drug within 14 days of enrollment

 -  Known hypersensitivity to thalidomide or lenalidomide

 -  Known hypersensitivity to Velcade, boron, or mannitol

 -  The development of erythema nodosum as characterized by desquamating rash while taking
 thalidomide or similar drugs

 -  Concurrent use of other anti-cancer agents or treatment

 -  Known positive for HIV

 -  Diagnosed or treated for a non-hematologic malignancy within 2 years of enrollment,
 with the exception of complete resection of basal cell carcinoma or squamous cell
 carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after
 curative therapy.

 -  Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
 require concurrent radiotherapy (which must be localized in its field size) should be
 deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
 date of therapy.