Clinical trial NCT00481832
Conditions: Lymphoma, Non-Hodgkin
Sponsor: Stanford University
Start date: 2007-01-01; Completion date: 2017-03-30
Enrollment: 50 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.

Detailed description:
Currently, patients with recurrent or primary refractory non-Hodgkin's lymphoma are treated with second-line chemotherapy (usually 2-3 courses) for the purpose of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells are mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. The standard high dose regimen consists of augmented carmustine, etoposide and cyclophosphamide. Unfortunately, there are subgroups of patients with poor outcomes using autologous transplantation including those with transformed lymphoma as well as patients who do not attain a minimal disease state due to chemoresistant disease.

These groups of patients have limited disease control and survival with standard chemotherapy regimens, and although they often have excellent cytoreduction with the high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The current trial utilizes a similar approach that has been taken with patients with multiple myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a combined autologous and non-myeloablative allogeneic transplant regimen to reduce transplant-related complications. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide and cyclophosphamide with autologous hematopoietic cell support as a method of cytoreduction. Approximately 60-120 days after the autologous transplant, patients will receive an allogeneic transplant using a preparative regimen of total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a graft-versus-lymphoma effect.

Arms: arm 1: A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Interventions: intervention 1: Cyclophosphamide intervention 2: BCNU intervention 3: Etoposide intervention 4: Filgrastim intervention 5: Antithymocyte globulin intervention 6: Cyclosporine intervention 7: Mycophenolate mofetil intervention 8: Rituximab intervention 9: Autologous hematopoietic stem cell transplantation (auto-HSCT) intervention 10: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) intervention 11: Total lymphoid irradiation intervention 12: CD34+ Cells intervention 13: Solu-Medrol
Intervention descriptions: intervention 1: 4 gm /m² IV over 2 hours on day 8 intervention 2: The dose of BCNU will be based on actual body weight unless the actual body weight is more than 15 kg greater than the ideal body weight in which case the adjusted ideal body weight will be used:

Males IBW = 50 kg + 2.3 kg/inch over 5 feet Females IBW = 45.5 kg + 2.3 kg/inch over 5 feet Adjusted IBW = IBW + 50% (actual weight - IBW) intervention 3: 60mg/kg, IV over 4 hours on day -4 pre-transplant and for preparative regimen. The dose of etoposide for mobilization is 2 gm/ m². intervention 4: 10µg/kg sc qd starting day following cyclosphamide (or VP-16) until last day of apheresis intervention 5: 1.5 mg/kg/d, IV from day -11 to -7 intervention 6: 5mg/kgbid,variable, po or IV intervention 7: 15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. Thereafter, beginning on day +1 MMF is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched donor. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be stopped on day +28 for matched related donors. For one antigen mismatched related or unrelated donors, the taper will begin on day +40. MMF will be tapered by 10% weekly till off, typically by day +96. If there is nausea and vomiting at any time preventing the oral administration of MMF, MMF should be administered intravenously at an equal dose. MMF dosing is based on actual body weight. intervention 8: 375 mg/m2 IV (calculated based on actual body weight) on day 1 and day 7. Administered per current standard of care.. intervention 9: Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents intervention 10: Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF) intervention 11: TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT intervention 12: 2 x 10e6 CD34+ cells per kg actual body weight on Day 0 intervention 13: 1 mg/kg, Day-11 to Day-7

Protocol documents: