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Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

Phase 2
18 Years
70 Years
Open (Enrolling)
Lymphoma, Non-Hodgkin

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Trial Information

Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

Currently, patients with recurrent or primary refractory non-Hodgkin's lymphoma are treated
with second-line chemotherapy (usually 2-3 courses) for the purpose of cytoreduction and to
establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells are
mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and
cryopreserved. The standard high dose regimen consists of augmented carmustine, etoposide
and cyclophosphamide. Unfortunately, there are subgroups of patients with poor outcomes
using autologous transplantation including those with transformed lymphoma as well as
patients who do not attain a minimal disease state due to chemoresistant disease.

Past studies conducted at Stanford have included a group of 17 patients with transformed
lymphoma who received autologous transplants, the median EFS and OS were 1.48 and 2.7 years
respectively with a 7-year survival of only 20%. In comparison, patients with chemosensitive
follicular lymphoma who received the same regimen also had a poor median EFS of 1.3 years,
but the median survival was 6.7 years. The outcomes for patients with
chemotherapy-resistant relapsed NHL is also poor with EFS in the range of 20% in many
studies of autologous transplantation.

These groups of patients have limited disease control and survival with standard
chemotherapy regimens, and although they often have excellent cytoreduction with the
high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The
current trial utilizes a similar approach that has been taken with patients with multiple
myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a
combined autologous and non-myeloablative allogeneic transplant regimen to reduce
transplant-related complications. Eligible patients will be treated with high-dose
chemotherapy using BCNU, etoposide and cyclophosphamide with autologous hematopoietic cell
support as a method of cytoreduction. Approximately 60-120 days after the autologous
transplant, patients will receive an allogeneic transplant using a preparative regimen of
total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a
graft-versus-lymphoma effect.

Inclusion Criteria:

- Age 18 to 70 years.

- Histologically proven non-Hodgkin's lymphoma

- 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. Eligible patients must have 1) transformed
lymphoma, 2) mycosis fungoides that is resistant or refractory to therapy, 3) other
histological subtypes in patients that do not have adequate cytoreduction to salvage
chemotherapy to reach a minimal disease state, 4) patients in 2nd or greater relapse
or 3 or subsequent remission, or 5) other patients with non-Hodgkin's lymphoma felt
to have less than a 20% chance of event-free survival with autologous transplant
after discussion with the BMT Faculty and the Principal Investigator

- Definition of Minimal Disease State- No individual lymph nodes greater than 2
cm, greater than >75% reduction in a bulky mass (> 10 cm) and < 10% bone marrow
involvement with lymphoma.

- ECOG performance status < 2

- Matched related or unrelated donor identified and available. Donor must be a
complete match or have only a single allele mismatch.

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

- Women of child-bearing potential and sexually active males must 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 = (140Óage)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 must have an echocardiogram or MUGA scan within 42 days of registration. If
the ejection fraction is < 40%, the patient will not be eligible. If the ejection
fraction is 40-50%, patients must have an exercise echocardiogram or dobutamine-echo
with a normal response to exercise.

- Patients must have a corrected diffusion capacity > 50% prior to the autologous
transplant and > 40% prior to the allogeneic transplant.

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

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 active infection requiring oral or intravenous antibiotics are

- No prior autologous or allogeneic hematopoietic cell transplantation.

- No prior radioimmunotherapy

- Patient with recurrent/refractory diffuse large B cell lymphoma.

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.

- Virology testing including CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be
performed within 30 days of donation.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Outcome Time Frame:

Two years after the last participant is enrolled.

Safety Issue:


Principal Investigator

Wen-Kai Weng

Investigator Role:

Principal Investigator

Investigator Affiliation:

Stanford University


United States: Institutional Review Board

Study ID:




Start Date:

January 2007

Completion Date:

December 2013

Related Keywords:

  • Lymphoma, Non-Hodgkin
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Stanford University School of Medicine Stanford, California  94305-5317