Clinical trial NCT00482053
Conditions: Lymphoma, B-cell Lymphoma, Non-Hodgkin Diffuse Large B-cell Lymphoma (DLBCL) Malignant Lymphoma, Non-Hodgkin
Sponsor: Stanford University
Start date: 2006-10-01; Completion date: 2010-05-01
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to determine if double autologous then allogeneic hematopoietic cell transplant may offer an improved treatment option for patients with relapsed diffuse large B-cell lymphoma (DLBCL) who are not likely to be cured by the conventional transplantation regimen.

Detailed description:
This study tests a tandem transplant approach that starts with transplantation of the participant's own hematopoietic (blood) cells, eg, autologous hematopoietic cell transplant (auto-HCT) as preparation for an subsequent matched-donor allogeneic HCT (allo-HCT).

Participants will be have progenitor cells (stem cells) mobilized into the peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim (G-CSF); undergo apheresis to collect autologous peripheral blood stem cells (PBSC, aka hematopoietic cells); and be re-infused with ≥ 3 x 10e6 CD34+ cells/kg (auto-HCT). Subsequently, participants will receive therapeutic, non-myeloablative chemotherapy (carmustine + cyclophosphamide + etoposide), then transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by ≥ 2 x 10e6 CD34+ cells/kg allogeneic PBSC obtained from a human leukocyte antigen (HLA)-matched or HLA single allele / antigen-mismatched donor (allo-HCT). Donors will be mobilized with 16 µg/kg filgrastim. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT infusion treatment includes cyclosporine and mycophenolate mofetil (MMF)

Subject's participation ends if a suitable matched donor is not identified within the 150 days.

Pre-medication treatments administered during this study may include acetaminophen; diphenhydramine; hydrocortisone; and methylprednisolone.

Arms: arm 1: Participants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT).

Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning \[total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)\] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF).

Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Interventions: intervention 1: Autologous hematopoietic stem cell transplantation (auto-HSCT) intervention 2: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) intervention 3: Total lymphoid irradiation (TLI) intervention 4: Rituximab intervention 5: Carmustine intervention 6: Etoposide intervention 7: Filgrastim intervention 8: Anti-thymocyte globulin (ATG) intervention 9: Cyclosporine intervention 10: Mycophenolate mofetil (MMF) intervention 11: Cyclophosphamide intervention 12: Acetaminophen intervention 13: Diphenhydramine intervention 14: Hydrocortisone intervention 15: Methylprednisolone
Intervention descriptions: intervention 1: Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents intervention 2: Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF) intervention 3: TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT intervention 4: 375 mg/m2 IV days 1 and 7 over 4 to 8 hours intervention 5: Based on body weight, unless its more than 15 kg greater than the idal body 15mg/kg (max dose 550 mg/m2) day -6 over 2 hours.

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 6: 60 mg/kg over 4 hours day -4 and alternatively VP-16 2 Gm/m² may be used (for mobilization) intervention 7: 10 µg/kg/day subcutaneous starting Day 9 until last day of apheresis. 5 ug/kg actual body weight per day will be started at Day +6 after allo-HCT until hematologic recovery intervention 8: 1.5 mg/kg/day for 5 days intervention 9: 5.0 mg/kg twice daily from day -3 until after day +56 intervention 10: 250 mg (total) twice daily, oral

15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. 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. intervention 11: 100 mg/kg will be administered over 2 hours on day -2 intervention 12: Pre-medication for rituximab and PBPC infusion. Administered at 650 mg by mouth 1 hour prior to infusion intervention 13: Pre-medication for rituximab and PBPC infusion. Administered at 50 mg intravenous 1 hour prior to infusion intervention 14: Pre-medication for the PBPC infusion. Administered at 100 mg intravenous 1 hour prior to infusion intervention 15: Anti-reaction medication for the ATG infusion. Administered at 1 mg/kg, Day-11 to Day-7

Protocol documents: