Study Stopped
Low accrual
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
3 other identifiers
interventional
3
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Oct 2006
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2006
CompletedFirst Submitted
Initial submission to the registry
May 31, 2007
CompletedFirst Posted
Study publicly available on registry
June 4, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2010
CompletedResults Posted
Study results publicly available
May 14, 2018
CompletedMay 14, 2018
May 1, 2018
3.6 years
May 31, 2007
October 25, 2017
May 11, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Event-free Survival (EFS) Per Protocol
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.
48 months
Secondary Outcomes (6)
Median Time to Neutrophil Engraftment After Autologous Transplant
within 1 month
Median Time to Platelet Engraftment After Autologous Transplant
within 1 month
Median Time to Neutrophil Engraftment After Allogeneic Transplant
within 1 month
Median Time to Platelet Engraftment After Allogeneic Transplant
within 1 month
Incidence of Chronic Graft vs Host Disease (GvHD)
3 years
- +1 more secondary outcomes
Study Arms (1)
Auto-HCT followed by Allo-HCT for Poor-risk DLBCL
EXPERIMENTALParticipants 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
Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents
Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF)
TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT
375 mg/m2 IV days 1 and 7 over 4 to 8 hours
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)
60 mg/kg over 4 hours day -4 and alternatively VP-16 2 Gm/m² may be used (for mobilization)
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
1.5 mg/kg/day for 5 days
5.0 mg/kg twice daily from day -3 until after day +56
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.
100 mg/kg will be administered over 2 hours on day -2
Pre-medication for rituximab and PBPC infusion. Administered at 650 mg by mouth 1 hour prior to infusion
Pre-medication for rituximab and PBPC infusion. Administered at 50 mg intravenous 1 hour prior to infusion
Pre-medication for the PBPC infusion. Administered at 100 mg intravenous 1 hour prior to infusion
Anti-reaction medication for the ATG infusion. Administered at 1 mg/kg, Day-11 to Day-7
Eligibility Criteria
You may qualify if:
- 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
- +1 more criteria
You may not qualify if:
- 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.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Stanford University School of Medicine
Stanford, California, 94305, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Wen-Kai Weng, Assistant Professor of Medicine
- Organization
- Stanford University Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Wen-Kai Weng
Stanford University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor of Medicine
Study Record Dates
First Submitted
May 31, 2007
First Posted
June 4, 2007
Study Start
October 1, 2006
Primary Completion
May 1, 2010
Study Completion
May 1, 2010
Last Updated
May 14, 2018
Results First Posted
May 14, 2018
Record last verified: 2018-05
Data Sharing
- IPD Sharing
- Will not share