Know Cancer

forgot password

A Phase I Dose Escalating Study of Bortezomib and Lenalidomide in Patients With Untreated or Previously Treated, Primary and Secondary Non 5q- Del Myelodysplasia

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

A Phase I Dose Escalating Study of Bortezomib and Lenalidomide in Patients With Untreated or Previously Treated, Primary and Secondary Non 5q- Del Myelodysplasia

Currently, there are no curative therapies for myelodysplasia except for allogeneic stem
cell transplantation. Both lenalidomide and bortezomib have activity as single agents in
patients with myelodysplasia. This study proposes using bortezomib in cohorts of 3-6
patients at the doses of 0.7, 1, and 1.3 mg/m2 on days 1, 4, 8, and 11 to determine the MTD
in combination withlenalidomide 10 mg a day, for 21 days of a 28 day treatment cycle. The
planned bortezomib doses have been evaluated in previous Phase I clinical studies in similar
patient populations and have been safe and well tolerated in a twice-weekly schedule of
administration. Lenalidomide has been shown to have efficacy in myelodysplasia. The
combination of lenalidomide and bortezomib has been used in patients with multiple myeloma.

Inclusion Criteria:

- Patients may be untreated or previously treated.

- Age > 18 years

- Able to adhere to study schedule and other protocol requirements

- Unequivocal clinicopathologic diagnosis of myelodysplastic syndrome, non 5q-

- Patients may have had prior chemotherapy or radiotherapy for another malignancy or
myelodysplasia as long as it was completed at least 4 weeks (6 weeks for nitrosureas)
prior to initiation of therapy.

- ECOG performance status of 0-2 (Appendix 10.3)

- Life expectancy greater than 3 months

- Total bilirubin ≤ 2.0 mg/dl, ALT and AST ≤ 3 X the upper limit of normal (ULN),
creatinine < 2.0 mg/dl all within 28 days prior to enrollment.

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understanding that consent may be withdrawn by the subject at any time without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

- Absolute neutrophil count > 0.5 x 10 (9)/l

- Platelet count > 30 x 10 (9)/l

- Prior treatment with 5-azacytidine is encouraged, but not required.

- Patients may have had prior treatment for MDS, including single agent lenalidomide or

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50mIU/ml within 10-14 days prior to and
within 24 hours of prescribing lenalidomide and must commit to abstinence from
heterosexual intercourse or begin TWO acceptable methods of birth control,at least 4
weeks before starting taking lenalidomide. FCBP must agree to ongoing pregnancy
testing. Men must agree not to father a child and agree to use a latex condom during
sexual contact with a female of child bearing potential even if they have had a
successful vasectomy.

- All study participants must be registered into the mandatory RevAssist Program®, and
be willing and able to comply with the requirements of RevAssist®.

Exclusion Criteria:

- Ejection fraction < 40%

- Patients who have had a myocardial infarction within 6 months of enrollment or has
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

- 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 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 the 28 days prior to trial enrollment.

- Patients with ≥ Grade 2 peripheral neuropathy or active herpes infection

- Patients with an 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

- Patients with secondary MDS that require concurrent therapy for the primary cancer

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

- Patient with hypersensitivity to bortezomib, boron or mannitol.

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

- Patient has received an investigational drug within 28 days of enrollment.

- Known hypersensitivity to thalidomide or lenalidomide

- Concurrent use of other anti-cancer agents or treatments.

- Known positive for HIV

Type of Study:


Study Design:

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

Outcome Measure:

Establish the maximally tolerated dose of bortezomib, up to 1.3 mg/m2/day, that can be administered in combination with lenalidomide in patients with primary and secondary non 5q del myelodysplasia who are untreated or previously treated.

Outcome Time Frame:

3, 6 and 9 months

Safety Issue:


Principal Investigator

Karen Ballen, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Institutional Review Board

Study ID:




Start Date:

November 2007

Completion Date:

March 2012

Related Keywords:

  • Myelodysplasia
  • Myelodysplasia
  • Myelodysplastic Syndromes
  • Preleukemia



Massachusetts General HospitalBoston, Massachusetts  02114-2617
Dana Farber Cancer InstituteBoston, Massachusetts  02115