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

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.

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.