Clinical trial NCT01373229
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Keywords: Chronic Lymphocytic Leukemia CLL
Sponsor: David Rizzieri, MD
Start date: 2012-01-01; Completion date: 2015-03-01
Enrollment: 21 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
In research studies, lenalidomide (also called Revlimid) has shown some response in chronic lymphocytic leukemia (CLL); however, responses are usually partial responses that occur after several months of taking the study drug. It is thought that by adding the drug plerixafor (also called Mozobil) responses may be improved and/or occur sooner.

The main purpose of this study is to determine the dose of plerixafor that is safe to use in combination with lenalidomide. The study will also look at the response rates of the combination of lenalidomide and plerixafor and the effect the study drugs have on CLL cells.

Detailed description:
The combination of lenalidomide and plerixafor will be evaluated in this single institution, open label clinical study of subjects with relapsed chronic lymphocytic leukemia (CLL). The overall design of the phase 1 study includes up to three treatment "stages."

Each subject will receive lenalidomide 5mg by mouth daily beginning on cycle 1 day 1. If tolerated, the dose will be increased by 2.5mg every 7 days to a maximum dose of 10mg by mouth daily (Stage 1). Once the subject is stably maintained on a daily dose of lenalidomide of 10mg daily and the white blood cell (WBC) count is \<100.0 x 109 / L, and has been taking lenalidomide for at least 28 days, plerixafor will be added (Stage 2). In the dose escalation phase, 4 different doses of plerixafor in combination with lenalidomide will be studied in cohorts of 3 to 6 subjects each, following a standard "3 + 3" format:

* Cohort 1: plerixafor 0.24 mg/kg subcutaneous (SC) daily thrice weekly (Mon, Wed, Fri)
* Cohort 2: plerixafor 0.32 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
* Cohort 3: plerixafor 0.42 mg/kg SC daily thrice weekly (Mon, Wed, Fri)
* Cohort 4: plerixafor 0.54 mg/kg SC daily thrice weekly (Mon, Wed, Fri) Plerixafor will be administered for 3 weeks of each cycle (days 1, 3, 5, 8, 10, 12, 15, 17, and 19) followed by a 1 week rest period. Lenalidomide dosing will be continuous.

An interim assessment of response will be performed after 4 cycles of combination therapy:

* Subjects achieving a complete response (CR) by National Cancer Institute (NCI)-96 criteria will continue lenalidomide monotherapy (plerixafor is discontinued) until disease progression.
* Subjects achieving a partial response (PR) will continue both lenalidomide and plerixafor. Additionally, rituximab 375mg/m2 will be added on day 1 of each subsequent cycle beginning with cycle 5, day 1 of combination therapy. (Stage 3). Treatment with the combination of lenalidomide and plerixafor will continue for a maximum of 12 cycles of combination therapy. Subjects may receive up to 8 doses of rituximab concurrent with lenalidomide and plerixafor on day 1 of each cycle. Subjects will then continue single agent lenalidomide until disease progression.
* Subjects with stable disease may continue lenalidomide and plerixafor at the discretion of the investigator and the subject. Rituximab 375 mg/m2 will be added on day 1 of each subsequent cycle. Treatment, dose, schedule, and duration are the same as for subjects achieving a PR.

Arms: arm 1: 1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:

   * Cohort 1: 0.24 mg/kg
   * Cohort 2: 0.32 mg/kg
   * Cohort 3: 0.42 mg/kg
   * Cohort 4: 0.54 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
Interventions: intervention 1: Lenalidomide + Plerixafor (+ Rituximab)
Intervention descriptions: intervention 1: 1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:

   * Cohort 1: 0.24 mg/kg
   * Cohort 2: 0.32 mg/kg
   * Cohort 3: 0.42 mg/kg
   * Cohort 4: 0.54 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.

Protocol documents: