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Phase II Poor Risk Diffuse Large B-cell Lymphoma (DLBCL) of Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) Followed by Matched Allogeneic Hematopoietic Transplantation as Consolidation to Autologous Hematopoietic Cell Transplantation (AHCT)

Information source: Stanford University
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Lymphoma, B-Cell; Blood and Marrow Transplant (BMT); Lymphomas: Non-Hodgkin; Diffuse Large B-Cell

Intervention: Total lymphoid irradiation (TLI) (Procedure); Anti-thymocyte globulin (ATG) (Drug); Allogeneic hematopoietic cell transplantation (Procedure); Autologous hematopoietic cell transplantation (AHCT) (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: Stanford University

Official(s) and/or principal investigator(s):
Sandra Jeane Horning, Principal Investigator, Affiliation: Stanford University


The purpose of this study is to develop an alternative treatment for patients with relapsed diffuse large B cell lymphoma who are not likely to be cured by the conventional transplantation regimen.

Clinical Details

Official title: A Phase II Study in Poor Risk Diffuse Large B-cell Lymphoma (DLBCL) of Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) Followed by Matched Allogeneic Hematopoietic Transplantation as a Consolidation to Autologous Hematopoietic Cell Transplantation (AHCT)

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

To evaluate the kinetics of donor hematopoietic cell engraftment and chimerism.

To evaluate the incidence and extent of chronic GVHD.

To evaluate the overall and transplant related mortality rate.

Detailed description: This purpose of this clinical trial is to develop an alternative treatment for patients with relapsed diffuse large B cell lymphoma 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 patient's own hematopoietic (blood) cells (AHCT) as preparation for an allogeneic transplantation whereby the blood cells from a matched donor are used to try to support the patient's immune system to fight the cancer cells. A novel combination of lymphoma-specific radiation that only impacts the lymphoid organs (lymph nodes and spleen) and an immune suppressing drug is given to prepare the patient body to receive the donor's cells. This conditioning regimen is used because it has been shown to reduce the likelihood of a very common side-effect, known as graft versus host disease, a negative reaction of the donor's cells against the patient's tissues. By carefully preparing the patient for this immune-based strategy, it is hoped that an improvement in event-free survival and a reduction in the risk of disease relapse after AHCT will be seen.


Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.


Inclusion Criteria:- Age 18 to 70 years.

- Histologically proven diffuse large B-cell lymphoma (DLBCL) by the WHO


- Relapse after achieving initial remission or failure to achieve initial remission.

Patients with residual radiographic abnormalities after primary therapy are eligible if abnormalities are FDG-PET positive.

- 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.

- ECOG performance status < 2

- Matched related or unrelated donor identified and available

- Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration

- Women of child-bearing potential and sexually active males are strongly advised to

use an accepted and effective method of birth control.

- Patients must have a pretreatment serum bilirubin < 2 x the institutional ULN, a

serum creatinine < 2 x the institutional ULN and measured or estimated creatinine clearance > 60 cc/min by the following formula (all tests must be performed within 28 days prior to registration):

- Estimated Creatinine Clearance = (140 age)X WT(kg) X 0. 85 if female 72X serum


- Patients must have an EKG within 42 days prior to registration that shows no

significant abnormalities that are suggestive of active cardiac disease.

- Patients requiring therapy for coronary artery disease, cardiomyopathy, dysrhythmia,

or congestive heart failure are not eligible.

- 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.

- Patients must have a corrected diffusion capacity >55%.

- Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis

with cyclophosphamide are not eligible.

- Patients with > grade 2 sensory or motor peripheral neuropathy from prior vinca

alkaloid use are not eligible.

- Patients must be informed of the investigational nature of this study and must sign

and give written informed consent in accordance with institutional and federal guidelines. Exclusion Criteria:- Pregnant or breast-feeding women are ineligible due to the known birth defects association with the treatments used in this study.

- Patients known to be human immunodeficiency virus (HIV)-positive are ineligible

because the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population. The antibody test for HIV must be performed within 42 days of registration.

- No chemotherapy other than corticosteroids should be administered within 2 weeks of

the initiation of protocol therapy.

- No prior malignancy is allowed 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. Patients with a prior diagnosis of non-Hodgkin's lymphoma are not eligible.

- Patients with active infection requiring oral or intravenous antibiotics are


- No prior autologous or allogeneic hematopoietic cell transplantation.

- No prior radioimmunotherapy

Donor Selection/Evaluation:

- 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 CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be

performed within 30 days of donation.

- Prospective donors will be screened for CMV seroreactivity and seronegative donors

will be utilized if available. If the possibility of more than one HLA-matched related donor exists, then the donor will be selected on the basis of CD31 allotype.

Locations and Contacts

Stanford University School of Medicine, Stanford, California 94305, United States
Additional Information

Starting date: October 2006
Last updated: September 10, 2010

Page last updated: August 20, 2015

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