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A Phase II Trial of Revlimid® as Consolidation Treatment of Residual Disease in Patients With Chronic Lymphocytic Leukemia (CLL)

Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia

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Trial Information

A Phase II Trial of Revlimid® as Consolidation Treatment of Residual Disease in Patients With Chronic Lymphocytic Leukemia (CLL)

CLL is the most prevalent leukemia in the western world and is considered incurable.
Standard therapy for CLL is typically in the form of purine analogs, alkylating agents,
monoclonal antibodies, or combinations of these drugs. Unfortunately, despite high
response rates these treatment strategies are considered palliative and all patients
eventually experience disease relapse and with time become less responsive to therapy.
Following standard treatment, CLL patients often fail to achieve a complete response, or
they have minimal residual disease (MRD) in the marrow and this often correlates with a
short time to progression and next therapy.

The National California Institute Working Group and newly updated International Workshop on
Chronic Lymphocytic Leukemia Working Group definition of a complete response (CR) in CLL is
quite permissive and allows for the persistence of 30% of residual lymphocytes in the
marrow. These response criteria were initially developed at a time treatment options for
CLL patients were limited and relatively few CRs were obtained. However, therapeutic
advances including monoclonal antibodies and stem cell transplant have reduced residual CLL
cells to a greater extent than previously possible and necessitated updating of current
response criteria to include MRD evaluation and the development of highly sensitive assays
that can measure MRD such as multiparametric 4-color flow cytometry, allele-specific PCR,
and more convenient investigational assays such as peripheral blood levels of CLLU-1.
Regardless, the majority of complete responses achieved following any initial therapy still
have detectable residual disease.

Importantly, CLL patients who lack minimal residual disease following treatment consistently
demonstrate prolonged progression free survival (PFS) and overall survival (OS) compared
with those with persistent MRD. As such, the development of therapeutic strategies that
have the potential to eradicate disease after therapy are highly desired. Such
consolidation therapies have potential to improve the depth of a remission, prolong PFS, and
potentially overall survival in CLL patients. The investigators propose that Revlimid
might be one such therapy that can be used as consolidation to eradicate residual disease or
improve remissions in patients who have received therapy and that this might lead to a
prolonged disease free duration. The investigators hypothesize that Revlimid will be safe
and well tolerated in this setting.

The investigators further hypothesize that Revlimid consolidation might be effective in CLL
patients at risk of early relapse such as those patients with leukemia cells that use
unmutated immunoglobulin heavy chain variable regions. The investigators found that the
relative CLLU1 expression level on blood samples mirrored the residual level of CLL cells as
determined by 4-color flow cytometry on cells from the aspirated marrow. The investigators
hypothesize that monitoring for expression of CLLU1 might provide a reliable means with
which to evaluate residual disease in the context of Revlimid consolidation therapy.
Previous single agent Revlimid studies have suggested that Revlimid treatment of CLL
patients may positively impact immune parameters increasing the relative composition of
T-lymphocytes, modulation of cytokines, and can lead to improvement immunoglobulin levels
and or the development of leukemia specific antibodies, the investigators hypothesize that
similar changes in immune parameters may occur in the context of Revlimid consolidation

Inclusion Criteria:

- Diagnosis of chronic lymphocytic leukemia:

- Previously treated patients of any age with a diagnosis of CLL with documented
residual disease following therapy, but not meeting an indication for treatment based
on current guidelines

- At least 2 months following previous CLL directed therapy

- ECOG performance status of less than or equal to 2 at study entry

- Laboratory test results within these ranges:

- Platelet count greater than or equal to 50 x 109/L

- CrCl >.60 ml/min

- Total bilirubin less than or equal to 1.5 mg/dL

- AST (SGOT) and ALT (SGPT) less than or equal to 2 x ULN

- Females of childbearing must adhere to strict guidelines and have negative pregnancy
test prior to enrollment

- Understand and voluntarily sign an informed consent form.

- Age greater than or equal to 18 years at the time of signing the informed consent

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

- Disease free of prior malignancies for greater than or equal to 2 years with
exception of currently treated basal cell, squamous cell carcinoma of the skin, or
carcinoma in situ" of the cervix or breast.

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

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to aspirin may use warfarin or low molecular weight heparin).

Exclusion Criteria:

- Known Hepatitis B Ag positive, Hepatitis C positive patients.

- Known HIV positive patients.

- Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune
thrombocytopenia (ITP)

- Patients with active fungal, bacterial, and/or viral infection

- Patients with known hypersensitivity to Revlimid or thalidomide

- Concurrent use of other anti-cancer agents or treatments

- Patients with history of deep venous thrombus or pulmonary embolism

- Patients who are at increased risk of thrombosis during treatment with Revlimid
including those taking concurrent erythropoietin, darbepoetin or high-dose

- Inability to provide informed consent.

- Concurrent malignancy (excluding basal and squamous cell skin cancers).

- Pregnant or breast-feeding females. (Lactating females must agree not to breast feed
while taking Revlimid).

- 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 28 days of baseline.

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

- Patients with a history of embolic events (e.g. TIA) from arrhythmia or peripheral
arterial disease or of recent MI whether or not treated with anti-platelet drug.

Type of Study:


Study Design:

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

Outcome Measure:

Eradication of residual disease from the marrow

Outcome Time Frame:

From date of first dose until then end of 12 cycles of treatment (12 months) or progression of disease, whichever comes first.

Safety Issue:


Principal Investigator

Thomas J. Kipps, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California Medical Center


United States: Institutional Review Board

Study ID:




Start Date:

November 2011

Completion Date:

November 2015

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Chronic
  • Lymphocytic
  • Leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



Moores UCSD Cancer Center La Jolla, California  92093-0658