Pentostatin, Cyclophosphamide, and Rituximab Followed By Campath-1H in Patients With Relapsed or Refractory B-Cell CLL
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|ClinicalTrials.gov Identifier: NCT00074282|
Recruitment Status : Completed
First Posted : December 11, 2003
Results First Posted : February 27, 2019
Last Update Posted : November 17, 2020
RATIONALE: Drugs used in chemotherapy, such as pentostatin, cyclophosphamide, and CAMPATH-1H 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 CAMPATH-1H work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Biological: rituximab Drug: cyclophosphamide Drug: pentostatin Drug: Alemtuzumab||Phase 2|
- 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 CAMPATH-1H .
- Determine the presence of minimal residual disease in patients treated with this regimen who achieve a CR or nPR
- Determine the toxicity of this regimen in these patients.
- 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 CAMPATH-1H .
- 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 CAMPATH-1H, 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 CAMPATH-1H treatment and assess any association with clinical outcome and toxicities.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||102 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||December 16, 2004|
|Actual Primary Completion Date :||December 9, 2017|
|Actual Study Completion Date :||May 6, 2018|
Experimental: Arm A (PCR)
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. Cyclophosphamide given at 600 mg/m2 IV over 30-60 minutes in 250 mL NS on day 1 every 4 weeks of cycle 1-6.
Other Name: Rituxan
Other Name: Cytoxan
Experimental: Arm B (Alemtuzumab: CR, nPR)
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
Experimental: Arm C (Alemtuzumab: PR, <PR, PD)
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 to complete all 6 cycles of PCR to go on to Arm C, however, completing a minimum of 2 cycles was required.
- Response Rate [ Time Frame: 8 weeks after Cycle 6 ]Percent with response (CR, nPR, PR) with two-stage 90% confidence interval
- Molecular Complete Remission (MCR) Rate [ Time Frame: 3 months post alemtuzumab ]Percent of patients who have MCR (clinical CR with flow negative and RT-PCR negative)
- Overall Survival (OS) [ Time Frame: Up to 5 years from registration ]OS is defined as the time from registration until death from any cause.
- Progression-free Survival (PFS) [ Time Frame: Up to 5 years from registration ]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.
- 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 Campath-1H [ Time Frame: From re-registration up to 5 years (followed for response until progression) ]
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
|Study Chair:||Sanford J. Kempin, MD||Beth Israel Medical Center|