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Boulder, Colorado 80301

  • Leukemia

Purpose:

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 summary:

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.


Criteria:

Inclusion criteria: - 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 - 18 and over - ECOG 0-2 - Bilirubin no greater than 2 mg/dL (unless secondary to tumor, hemolysis, or Gilbert syndrome) - Creatinine no greater than 2.0 mg/dL - Creatinine clearance ≥ 30 mL/min - 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 - At least 8 weeks since prior rituximab - 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 Exclusion criteria: - Bone marrow dysplasia related to prior therapy - New York Heart Association class III or IV heart failure - Prior lenalidomide - Other malignancy within the past 2 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix - Pregnant or nursing - Concurrent oral or IV antibiotics for active infection


Study is Available At:


Original ID:

CDR0000343796


NCT ID:

NCT00074282


Secondary ID:

ECOG-2903


Study Acronym:


Brief Title:

Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL


Official Title:

Phase II Trial of Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Campath-1H for Previously Treated Relapsed or Refractory Patients With Chronic Lymphocytic Leukemia


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

120 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Eastern Cooperative Oncology Group


Oversight Authority:

Unspecified


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

3


Number of Groups:

0


Total Enrollment:

102


Enrollment Type:

Actual


Overall Contact Information

Official Name:Sanford J. Kempin, MD
Study Chair
Beth Israel Medical Center

Study Dates

Start Date:December 16, 2004
Completion Date:May 6, 2018
Completion Type:Actual
Primary Completion Date:August 28, 2013
Primary Completion Type:Actual
Verification Date:February 2019
Last Changed Date:February 6, 2019
First Received Date:December 10, 2003
First Results Date:February 6, 2019

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Progression-free Survival (PFS)
Time Frame:Up to 5 years from registration
Safety Issues:False
Description:PFS is defined as the time from registration until induction failure, institution of non-protocol therapy, relapse or death from any cause in the absence of relapse.
Outcome Type:Secondary Outcome
Measure:Overall Survival (OS)
Time Frame:Up to 5 years from registration
Safety Issues:False
Description:OS is defined as the time from registration until death from any cause.
Outcome Type:Primary Outcome
Measure:Molecular Complete Remission (MCR) Rate
Time Frame:3 months post alemtuzumab
Safety Issues:False
Description:Proportion of patients who have MCR (clinical CR with flow negative and RT-PCR negative)
Outcome Type:Primary Outcome
Measure:Response Rate
Time Frame:8 weeks after Cycle 6
Safety Issues:False
Description:Proportion with response (CR, nPR, PR)

Study Interventions

Intervention Type:Biological
Name:rituximab
Arm Name:Arm A (PCR)
Other Name:Rituxan
Intervention Type:Drug
Name:cyclophosphamide
Arm Name:Arm A (PCR)
Other Name:Cytoxan
Intervention Type:Drug
Name:pentostatin
Arm Name:Arm A (PCR)
Other Name:deoxycoformycin
Intervention Type:Drug
Name:Alemtuzumab
Arm Name:Arm B (Alemtuzumab: CR, nPR)
Other Name:Campath

Study Arms

Study Arm Type:Experimental
Arm Name:Arm A (PCR)
Description:Treatment consisted of 6 cycles of pentostatin, cyclophosphamide, and rituximab (PCR) given every 28 days. Rituximab administered as follows: For the first infusion, all patients receive 100 mg dose (regardless of weight/BSA). For subsequent infusions, all patients receive rituximab 375 mg/m2. Pentostatin and cyclophosphamide administered as follows: Pentostatin given at 4 mg/m2 either as an IV push or IV over 10-30 minutes in 250 mL NS or D5W on day 1 every 4 weeks of cycles 1-6. Cyclophospha
Study Arm Type:Experimental
Arm Name:Arm B (Alemtuzumab: CR, nPR)
Description:Patients who achieved a confirmed CR or nPR, were registered to receive Alemtuzumab (Arm B). When the patient was registered to Arm B, the drug was administered three times a week for four weeks. The dose was 30 mg per dose. A twelve-week treatment-free period had to elapse before CAMPATH-1H began following completion of PCR for Arm B patients
Study Arm Type:Experimental
Arm Name:Arm C (Alemtuzumab: PR, <PR, PD)
Description:For those patients not achieving a CR or nPR (thus patients either achieved PR, SD, or PD), Alemtuzumab (Arm C) was administered three times a week for eighteen weeks at a dose of 30 mg TIW. For PR, SD and PD patients, the timing of CAMPATH-1H was left to the discretion of the investigator, and treatment could begin earlier but no less than two weeks and no longer than eight weeks after the completion of the last PCR course. Patients determined to have PD during treatment with PCR did not need t

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Eastern Cooperative Oncology Group
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation: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.
Reference Type:Results Reference
Citation: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.

Data Source: ClinicalTrials.gov

Date Processed: April 03, 2020

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