Clinical Trials Logo

Clinical Trial Summary

Primary objective of the study is to determine the maximum tolerated dose (MTD) of bortezomib (Velcade) in combination with rituximab, ifosfamide, carboplatin and etoposide for adult patients with relapsed or refractory aggressive B-cell lymphoma. The secondary objectives are to assess the tolerability and safety, the response rate, rate of autologous stem cell transplant and CD34+ progenitor cell collection and engraftment after treatment with this regimen.


Clinical Trial Description

Once subjects are determined to be eligible and informed consent is obtained,patients will be enrolled into a starting dose cohort of 1.0mg/m2. Based upon a satisfactory safety profile, additional patients will be enrolled into the 1.3, 1.5 and 1.7mg/m2 cohorts. Each of these dosing cohorts will only be enrolled if satisfactory safety profiles in each of the lower dosing cohorts are obtained. As the process continues, multiple cohorts will be receiving various dosing regimens simultaneously. If a DLT occurs in ≥2 out of 6 patients at the initial dose level, then 3 more patients will be accrued at dose level -1 (0.7mg/m2).

Bortezomib will be given on days 1 (prior to rituximab) and 4, rituximab 375 mg/m2 on day 1, carboplatin AUC 5 and ifosfamide with mesna, each 5 gm/m2, on day 3 and etoposide 100 mg/ m2/day on days 2, 3 and 4 of a 21-day cycle. They will also receive filgrastim on days 6-13 or pegfilgrastim on day 6. Dose-limiting toxicities (DLT) include any grade 3 or 4 non-hematologic toxicities (except alopecia and grade 3 febrile neutropenia), grade 4 febrile neutropenia (life-threatening sepsis) and grade 4 neutropenia persisting past day 35 or grade 3 or 4 thrombocytopenia persisting past day 35.

If there is a DLT at a given bortezomib dose level, 3 more subjects will be enrolled at that dose; if there are 2 or more DLTs then the MTD will be defined as the previous dose level. If at that dose level, >50% of subjects required bortezomib dose reduction, the MTD will be defined as the next lower dose level. Subjects will continue to be accrued in order to treat a minimum of 10 patients at the MTD.

Those who are candidates for autologous stem cell transplant will have CT scan of the neck, chest, abdomen and pelvis after 2 cycles. Subjects with PD or SD will be taken off study. Those with CR, PR or response not meeting PR criteria will undergo a total of 3 cycles of bortezomib + RICE. After the 3rd cycle of bortezomib + RICE, whole body PET/CT scan and bone marrow biopsy will be obtained.

Subjects who achieve CR or PR will then proceed to stem cell mobilization and collection by a standard regimen, followed by autologous stem cell transplant with a preparative regimen to be determined by the investigator. Those with SD or PD will be taken off study. While the mobilization and ASCT procedures are not part of the phase I protocol, outcomes of ASCT will be followed, including CD34+ progenitor cell collection, clinical response to transplant and survival.

Subjects who are not candidates for autologous stem cell transplant will have CT scan of the neck, chest, abdomen and pelvis after the 2nd and 4th cycles. Those who are responding will continue for a maximum of 6 cycles. ;


Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT01300793
Study type Interventional
Source University of California, San Francisco
Contact
Status Terminated
Phase Phase 1
Start date May 2007
Completion date April 2012

See also
  Status Clinical Trial Phase
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Completed NCT01878890 - Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure. Phase 1
Completed NCT04152148 - A Phase I Clinical Trial of BAT4306F on Safety, Tolerability and Pharmacokinetics for Patients Phase 1
Recruiting NCT05096234 - 18F-F-AraG PET Imaging to Evaluate Immunological Response to CAR T Cell Therapy in Lymphoma Phase 2
Recruiting NCT05191225 - Ultrafast Truxima Infusion in Non-Hodgkin's Lymphoma: Txagorapid Study Phase 4
Recruiting NCT05623982 - Phase Ib/II Study of GNC-038 Injection in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma Phase 1/Phase 2
Active, not recruiting NCT03664635 - MB-CART20.1 Lymphoma Phase 1/Phase 2
Recruiting NCT02356159 - Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Phase 1/Phase 2
Terminated NCT01699581 - Assessment of Impact Nutritional Program During Autologous Stem Cell Transplant Phase 2
Completed NCT01763398 - Analysis of the Risk Factors for the Neutropenic Fever in the High Risk NHL Patients for Developing Febrile Neutropenia Who Received 3-weekly CHOP-like Chemotherapy With Primary G-CSF Prophylaxis; Prospective Multicenter Observation Study N/A
Completed NCT01205503 - Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and Tumor Necrosis Factor Alpha (TNF-α) Release Phase 2
Completed NCT00975975 - Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer Phase 2
Completed NCT00969462 - Doxorubicin Pharmacokinetics and Response in Non Hodgkin's Lymphoma Phase 4
Completed NCT00659425 - CAT-8015 in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma Phase 1
Terminated NCT00475332 - Study to Treat Relapsed Follicular Non-Hodgkin's Lymphoma With Radiation and Bexxar Phase 2
Withdrawn NCT00577161 - Fludarabine, Pixantrone and Rituximab vs Fludarabine and Rituximab forRelapsed or Refractory Indolent NHL Phase 3
Completed NCT00608907 - An Open-Label Study to Assess the Effect of CYP3A4 Induction on the Pharmacokinetics of VELCADE (Bortezomib) Phase 1
Completed NCT00533728 - Safety of Soluble Beta-Glucan (SBG) in Treatment of Patients With Non-Hodgkin's Lymphoma Phase 1
Completed NCT00430352 - MAXIMA Study: A Study of Maintenance Therapy With MabThera (Rituximab) in Patients With Non-Hodgkin's Lymphoma. Phase 4
Completed NCT00581646 - Study of Psychosexual Impact of Cancer-Related Infertility in Women: Third Party Reproductive Assistance N/A