Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT
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| ClinicalTrials.gov Identifier: NCT00482053 |
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Recruitment Status :
Terminated
(Low accrual)
First Posted : June 4, 2007
Results First Posted : May 14, 2018
Last Update Posted : May 14, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma, B-cell Lymphoma, Non-Hodgkin Diffuse Large B-cell Lymphoma (DLBCL) Malignant Lymphoma, Non-Hodgkin | Procedure: Autologous hematopoietic stem cell transplantation (auto-HSCT) Procedure: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) Procedure: Total lymphoid irradiation (TLI) Drug: Rituximab Drug: Carmustine Drug: Etoposide Drug: Filgrastim Drug: Anti-thymocyte globulin (ATG) Drug: Cyclosporine Drug: Mycophenolate mofetil (MMF) Drug: Cyclophosphamide Drug: Acetaminophen Drug: Diphenhydramine Drug: Hydrocortisone Drug: Methylprednisolone | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 3 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 2 Study in Poor Risk Diffuse Large B-cell Lymphoma of Total Lymphoid Irradiation & Antithymocyte Globulin Followed by Matched Allogeneic Hematopoietic Transplantation as Consolidation to Autologous Hematopoietic Cell Transplantation |
| Study Start Date : | October 2006 |
| Actual Primary Completion Date : | May 2010 |
| Actual Study Completion Date : | May 2010 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Auto-HCT followed by Allo-HCT for Poor-risk DLBCL
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. |
Procedure: Autologous hematopoietic stem cell transplantation (auto-HSCT)
Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents
Other Name: Autologous peripheral blood progenitor cell (PBPC) transplantation Procedure: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF)
Other Name: Allogeneic peripheral blood progenitor cell (PBPC) transplantation Procedure: Total lymphoid irradiation (TLI) TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT Drug: Rituximab 375 mg/m2 IV days 1 and 7 over 4 to 8 hours
Other Names:
Drug: Carmustine 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) Other Names:
Drug: Etoposide 60 mg/kg over 4 hours day -4 and alternatively VP-16 2 Gm/m² may be used (for mobilization)
Other Names:
Drug: Filgrastim 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
Other Names:
Drug: Anti-thymocyte globulin (ATG) 1.5 mg/kg/day for 5 days Drug: Cyclosporine 5.0 mg/kg twice daily from day -3 until after day +56
Other Names:
Drug: Mycophenolate mofetil (MMF) 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. Other Name: CellCept Drug: Cyclophosphamide 100 mg/kg will be administered over 2 hours on day -2
Other Names:
Drug: Acetaminophen Pre-medication for rituximab and PBPC infusion. Administered at 650 mg by mouth 1 hour prior to infusion
Other Name: Tylenol Drug: Diphenhydramine Pre-medication for rituximab and PBPC infusion. Administered at 50 mg intravenous 1 hour prior to infusion
Other Name: Benadryl Drug: Hydrocortisone Pre-medication for the PBPC infusion. Administered at 100 mg intravenous 1 hour prior to infusion
Other Name: Cortef Drug: Methylprednisolone Anti-reaction medication for the ATG infusion. Administered at 1 mg/kg, Day-11 to Day-7
Other Name: Solu-Medrol |
- Event-free Survival (EFS) Per Protocol [ Time Frame: 48 months ]Event-free survival (EFS) through 4 years, as assessed in participants with poor-risk recurrent or primary refractory DLBCL treated with TLI and ATG followed by matched allogeneic hematopoietic cell transplantation as a consolidation to HCT. Event is defined as tumor progression or death.
- Median Time to Neutrophil Engraftment After Autologous Transplant [ Time Frame: within 1 month ]Reported as neutrophil engraftment after autologous transplant, defined as absolute neutrophil count (ANC) > 500/µL, counting from the day of transplant.
- Median Time to Platelet Engraftment After Autologous Transplant [ Time Frame: within 1 month ]Reported as platelet engraftment after autologous transplant, defined as platelet count > 20,000/µL, counting from the day of transplant.
- Median Time to Neutrophil Engraftment After Allogeneic Transplant [ Time Frame: within 1 month ]Reported as neutrophil engraftment after allogeneic transplant, defined as absolute neutrophil count (ANC) > 500/µL, counting from the day of transplant.
- Median Time to Platelet Engraftment After Allogeneic Transplant [ Time Frame: within 1 month ]Reported as platelet engraftment after allogeneic transplant, defined as platelet count > 20,000/µL, counting from the day of transplant.
- Incidence of Chronic Graft vs Host Disease (GvHD) [ Time Frame: 3 years ]The incidence of chronic graft vs host disease (GvHD) is reported as any events within 3 years. Note that GvHD was assessed per investigator judgement. There was no protocol-specified criteria of GvHD.
- Overall Survival (OS) [ Time Frame: 3 years ]To evaluate the overall and transplant related mortality rate, reported as the number of subjects remaining alive 3 years after transplant.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA
- Age 18 to 70 years.
- Histologically-proven diffuse large B-cell lymphoma (DLBCL) by the World Health Organization (WHO) classification.
- Relapse after achieving initial remission or failure to achieve initial remission. Patients with residual radiographic abnormalities after primary therapy are eligible if abnormalities are postive by fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET).
- Receipt of 2 cycles of second-line therapy and FDG-PET positive per Stanford (central) review. FDG-PET to be done 2 weeks after cycle 2 of second line chemotherapy.
- Eastern Cooperative Oncology Group (ECOG) performance status < 2
- Matched related or unrelated donor identified and available
- Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration
- Pretreatment serum bilirubin < 2 x the institutional upper limit of normal (ULN)
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Serum creatinine < 2 x the institutional ULN and measured or estimated creatinine clearance > 60 mL/min by the following formula (all tests must be performed within 28 days prior to registration):
- Estimated Creatinine Clearance = (140 age) x weight (kg) x 0.85 if female 72 x serum creatinine (mg/dL).
- EKG within 42 days prior to registration with no significant abnormalities suggestive of active cardiac disease
- Patients must have a radionuclide ejection fraction within 42 days of registration. If the ejection fraction is < 40%, the patient will not be eligible. If the ejection fraction is 40-50%, the patient will have a cardiology consult.
- Corrected diffusion capacity > 55%.
- Sexually active males are advised to use an accepted and effective method of birth control
- Women of child-bearing potential are advised to use an accepted and effective method of birth control
- Patients must sign and give written informed consent in accordance with institutional and federal guidelines. Patients must be informed of the investigational nature of this study.
EXCLUSION CRITERIA
- Known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide
- Greater than Grade 2 sensory or motor peripheral neuropathy from prior vinca alkaloid use
- Requiring therapy for coronary artery disease, cardiomyopathy, dysrhythmia, or congestive heart failure
- Known to be human immunodeficiency virus (HIV)-positive. The antibody test for HIV must be performed within 42 days of registration.
- Prior chemotherapy other than corticosteroids administered within 2 weeks of the initiation of protocol therapy.
- Prior malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patients has been disease-free for five years.
- Prior diagnosis of non-Hodgkin's lymphoma
- Active infection requiring oral or intravenous antibiotics
- Prior autologous or allogeneic hematopoietic cell transplantation
- Prior radioimmunotherapy
- Pregnant
- Lactating
DONOR ELIGIBILITY
- Related or unrelated HLA-identical donors who are in good health and have no contra-indication to donation
- No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 16 µg/kg of body weight.
- Donors will be evaluated with a full history and physical examination.
- Virology testing including HIV; cytomegalovirus (CMV); Epstein-Barr virus (EBV); human T-lymphotropic virus (HTLV); rapid plasma reagin (RPR); Hepatitis A, B and C be performed within 30 days of donation.
- Prospective donors will be screened for CMV seroreactivity and seronegative donors will be utilized if available.
- If more than one human leukocyte antigen (HLA)-matched related donor exists, then the donor will be selected on the basis of CD31 allotype.
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): NCT00482053
| United States, California | |
| Stanford University School of Medicine | |
| Stanford, California, United States, 94305 | |
| Principal Investigator: | Wen-Kai Weng | Stanford University |
| Responsible Party: | Wen-Kai Weng, Assistant Professor of Medicine, Stanford University |
| ClinicalTrials.gov Identifier: | NCT00482053 |
| Other Study ID Numbers: |
IRB-06703 97355 ( Other Identifier: Stanford University alternate IRB Number ) BMT186 ( Other Identifier: OnCore number ) |
| First Posted: | June 4, 2007 Key Record Dates |
| Results First Posted: | May 14, 2018 |
| Last Update Posted: | May 14, 2018 |
| Last Verified: | May 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Acetaminophen Diphenhydramine Promethazine Cyclosporine Mycophenolic Acid |
Methylprednisolone Methylprednisolone Hemisuccinate Hydrocortisone Cyclophosphamide Carmustine Rituximab Etoposide Cyclosporins Antilymphocyte Serum Lenograstim Sargramostim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |