ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00482053
Recruitment Status : Terminated (Low accrual)
First Posted : June 4, 2007
Results First Posted : May 14, 2018
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Wen-Kai Weng, Stanford University

May 31, 2007
June 4, 2007
October 25, 2017
May 14, 2018
May 14, 2018
October 2006
May 2010   (Final data collection date for primary outcome measure)
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.
To estimate event-free survival and toxicity in poor risk recurrent or primary refractory DLBCL treated with TLI and ATG followed by matched allogeneic hematopoietic cell transplantation as a consolidation to AHCT. [ Time Frame: 10 years ]
Complete list of historical versions of study NCT00482053 on ClinicalTrials.gov Archive Site
  • 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.
  • To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism. [ Time Frame: 10 years ]
  • To evaluate the incidence and extent of chronic GVHD. [ Time Frame: 10 years ]
  • To evaluate the overall and transplant related mortality rate. [ Time Frame: 10 years ]
Not Provided
Not Provided
 
Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT
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
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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Lymphoma, B-cell
  • Lymphoma, Non-Hodgkin
  • Diffuse Large B-cell Lymphoma (DLBCL)
  • Malignant Lymphoma, Non-Hodgkin
  • 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:
    • Rituxan
    • Mabthera
  • 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:
    • BCNU
    • BiCNU
  • Drug: Etoposide
    60 mg/kg over 4 hours day -4 and alternatively VP-16 2 Gm/m² may be used (for mobilization)
    Other Names:
    • Eposin
    • Etopophos
    • Vepesid
    • VP-16
  • 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:
    • Granulocyte colony-stimulating factor (G-CSF, GCSF)
    • Colony-stimulating factor 3 (CSF-3)
  • 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:
    • Cyclosporin
    • CSP
  • 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:
    • Cytoxan
    • Neosar
  • 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
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.

Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
3
30
May 2010
May 2010   (Final data collection date for primary outcome measure)

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)
  • 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.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00482053
IRB-06703
97355 ( Other Identifier: Stanford University alternate IRB Number )
BMT186 ( Other Identifier: OnCore number )
Yes
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
Plan to Share IPD: No
Wen-Kai Weng, Stanford University
Stanford University
Not Provided
Principal Investigator: Wen-Kai Weng Stanford University
Stanford University
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP