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Pentostatin, Cyclophosphamide, and Rituximab Followed By Lenalidomide in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00074282
Recruitment Status : Unknown
Verified November 2012 by National Cancer Institute (NCI).
Recruitment status was:  Recruiting
First Posted : December 11, 2003
Last Update Posted : November 12, 2012
Sponsor:
Collaborator:
Information provided by:

Study Description
Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Leukemia Biological: filgrastim Biological: pegfilgrastim Biological: rituximab Drug: cyclophosphamide Drug: lenalidomide Drug: pentostatin Phase 2

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Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Exploratory

  • 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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Masking: None (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
Study Start Date : December 2004
Estimated Primary Completion Date : October 2014


Arms and Interventions


Outcome Measures

Primary Outcome Measures :
  1. Response (CR, nPR, PR) rate in all patients treated with PCR
  2. Minimal-residual disease (MRD) as assessed by both flow cytometry and real-time allele-specific oligonucleotide polymerase chain reaction (RT-PCR)

Secondary Outcome Measures :
  1. Toxicity as measured by CTCAE criteria every month
  2. Overall survival and progression-free survival as measured by Kaplan-Meier method during study treatment
  3. 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

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria:

    • Peripheral blood absolute lymphocyte count greater than 5,000/mm^3
    • Lymphocytosis must comprise small to moderate size lymphocytes with no greater than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically
    • Phenotypically characterized CLL defined by the following:

      • Predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-cell markers (CD3 or CD2)
      • B cell expresses either kappa or lambda light chains
      • Surface immunoglobulin with low cell surface density expression
  • Requires chemotherapy, as indicated by any of the following:

    • Disease-related symptoms

      • Weight loss of 10% or more within the past 6 months
      • Extreme fatigue
      • Fevers greater than 100.5°F for 2 weeks without evidence of infection
      • Night sweats without evidence of infection
    • Evidence of progressive marrow failure manifested by the development of or worsening anemia (hemoglobin no greater than 10 g/dL) and/or thrombocytopenia (platelet count no greater than 100,000/mm^3)
    • Massive (i.e., greater than 6 cm below left costal margin) or progressive splenomegaly
    • Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or progressive adenopathy
    • Progressive lymphocytosis with an increase of greater than 50% over a 2-month period OR an anticipated doubling time of less than 6 months
  • Demonstrated progression after at least 1 course of either an alkylating agent-based or purine nucleoside-based (e.g., fludarabine) regimen OR failed to achieve a meaningful response OR relapsed after prior therapy

    • Patients who have relapsed after a pentostatin-based regimen are eligible provided the response was greater than 12 months prior to study entry
  • No bone marrow dysplasia related to prior therapy

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert syndrome)

Renal

  • Creatinine no greater than 2.0 mg/dL OR
  • Creatinine clearance ≥ 30 mL/min

Cardiovascular

  • No New York Heart Association class III or IV heart failure

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 methods of effective contraception (including 1 barrier method) for at least 28 days before starting lenalidomide, while participating in the study, and for at least 28 days after discontinuation/stopping lenalidomide
  • No other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Chemotherapy
  • At least 8 weeks since prior rituximab

Chemotherapy

  • See Disease Characteristics
  • At least 6 weeks since prior chemotherapy
  • At least 1 year since prior pentostatin, cyclophosphamide, and rituximab (PCR) therapy

    • PCR therapy at least 1 year prior to study entry allowed
  • No prior lenalidomide

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No concurrent oral or IV antibiotics for active infection
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00074282


  Show 145 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Sanford J. Kempin, MD Beth Israel Medical Center
OverallOfficial: Neil E. Kay, MD Mayo Clinic
More Information

Publications:
Kay NE, Kim HT, Kempin S, et al.: Predictors of clinical outcome to pentostatin, cyclophosphamide and rituximab (PCR) followed by campath for relapsed/refractory CLL : a study of the Eastern Cooperative Oncology Group, E2903. [Abstract] Blood 112 (11): A-1057, 2008.
Kempin S, Kay NE, Sun Z, et al.: Early results of pentostatin, cytoxan, rituximab (PCR) followed by CAMPATH-H (CA) for the treatment of relapse/refractory chronic lymphocytic leukemia (CLL) in ECOG protocol E2903. [Abstract] Blood 110 (11): A-3109, 2007.

Responsible Party: Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier: NCT00074282     History of Changes
Other Study ID Numbers: CDR0000343796
ECOG-2903
First Posted: December 11, 2003    Key Record Dates
Last Update Posted: November 12, 2012
Last Verified: November 2012

Keywords provided by National Cancer Institute (NCI):
refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Thalidomide
Rituximab
Lenalidomide
Pentostatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Leprostatic Agents
Anti-Bacterial Agents