Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT
Lymphoma, B-cell, Lymphoma, Non-Hodgkin, Diffuse Large B-cell Lymphoma (DLBCL)
About this trial
This is an interventional treatment trial for Lymphoma, B-cell
Eligibility Criteria
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.
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
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.