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

• Status: Terminated
• Trial end date: 2010-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Stanford University
• Collaborator: National Institutes of Health (NIH)
• Treatments: Acetaminophen; Antilymphocyte Serum; Carmustine; Cyclophosphamide; Cyclosporine; Cyclosporins; Diphenhydramine; Etoposide; Hydrocortisone; Lenograstim; Methylprednisolone; Methylprednisolone Hemisuccinate; Mycophenolic Acid; Promethazine; Rituximab; Sargramostim

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.