Pentostatin, Cyclophosphamide, and Rituximab Followed By Lenalidomide in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy, such as pentostatin, cyclophosphamide, and lenalidomide work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well pentostatin, cyclophosphamide, rituximab, and lenalidomide work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Lenalidomide for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia|
- Response (CR, nPR, PR) rate in all patients treated with PCR [ Designated as safety issue: No ]
- Minimal-residual disease (MRD) as assessed by both flow cytometry and real-time allele-specific oligonucleotide polymerase chain reaction (RT-PCR) [ Designated as safety issue: No ]
- Toxicity as measured by CTCAE criteria every month [ Designated as safety issue: Yes ]
- Overall survival and progression-free survival as measured by Kaplan-Meier method during study treatment [ Designated as safety issue: No ]
- Rate of molecular complete remission (MCR) after the treatment of PCR and alemtuzumab (before May 2011) or lenalidomide after May 2011) in patients who achieve a CR or nPR [ Designated as safety issue: No ]
|Study Start Date:||December 2004|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
- Determine the objective response rate (complete remission, partial remission [PR], or nodular PR) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab (PCR) followed by lenalidomide.
- Determine the presence of minimal residual disease in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Evaluate the toxicity of the combined therapy, PCR with lenalidomide, in patients with previously treated B-CLL.
- Determine the overall and progression-free survival of patients treated with this regimen.
- Evaluate the number of patients who after PCR (or during PCR for PD), only achieve a PR, SD, or PD and who subsequently convert to a higher response category after lenalidomide.
- Correlate V_H gene mutation status and CD38 expression of the CLL B-cell clones with clinical outcome in patients treated with this regimen.
- Correlate the differential expression of genes in the leukemic cells with clinical outcome in patients treated with this regimen.
- Correlate surface phenotype and genetic defects of the CLL B-cell clones with clinical outcome and gene expression patterns in patients treated with this regimen.
- Assess the angiogenic profile (i.e., secretion levels of pro- versus anti-angiogenic molecules) of CLL B cell clones as well as bone marrow angiogenesis (i.e., vascular density by immunohistochemistry) at baseline, after PCR, after lenalidomide, every six months (serum only), and at time of response assessment (marrow).
- Determine the V_H gene mutation status and CD38 expression of the B-CLL clones at study entry and at the end of the therapy and assess the association between the VH gene mutation status and CD38 expression and clinical outcome.
- Determine surface phenotype (by flow cytometry) and genetic defects (by CLL FISH panel) information on CLL-B cell clones and associate with clinical outcome.
- Monitor the T-cell status by repertoire and flow cytometry analysis to determine the nature and extent of T-cell deficiency induced by the PCR and lenalidomide treatment and assess any association with clinical outcome and toxicities.
OUTLINE: This is a multicenter study.
Pentostatin, cyclophosphamide, and rituximab (PCR)* therapy: Patients receive pentostatin IV over 10-30 minutes, cyclophosphamide IV over 30-60 minutes, and rituximab** IV on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 3 or pegfilgrastim SC on day 1 and continuing until blood counts recover. Treatment repeats every 28 days for a total of 6 courses in the absence of unacceptable toxicity.
NOTE: *Patients demonstrating progression while receiving PCR must have completed 2 courses of PCR prior to proceeding to lenalidomide therapy.
NOTE: **Patients receive rituximab IV on days 1, 3, and 5 for course 1 only; for courses 2-6, patients receive rituximab on day 1 only.
Lenalidomide*** therapy: Eight weeks after completion of PCR therapy or when diagnosed with progressive disease, patients receive lenalidomide orally (PO) on days 1-28. In the absence of disease progression or unacceptable toxicity, treatment repeats every 28 days for patients with partial remission (PR), stable disease, or progressive disease after PCR. Patients who achieve complete remission proceed to clinical observation.
NOTE: ***The alemtuzumab therapy was replaced by lenalidomide therapy in May, 2011.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 26-110 patients will be accrued for this study within 1.5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00074282
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|Study Chair:||Sanford J. Kempin, MD||Beth Israel Medical Center|
|Investigator:||Neil E. Kay, MD||Mayo Clinic|