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

Stanford University

Status and phase

Terminated

Phase 2

Conditions

Lymphoma, B-cell

Malignant Lymphoma, Non-Hodgkin

Diffuse Large B-cell Lymphoma (DLBCL)

Lymphoma, Non-Hodgkin

Treatments

Drug: Filgrastim

Drug: Etoposide

Procedure: Allogeneic hematopoietic stem cell transplantation (allo-HSCT)

Drug: Cyclophosphamide

Drug: Diphenhydramine

Drug: Anti-thymocyte globulin (ATG)

Drug: Carmustine

Drug: Mycophenolate mofetil (MMF)

Drug: Rituximab

Drug: Methylprednisolone

Drug: Acetaminophen

Procedure: Autologous hematopoietic stem cell transplantation (auto-HSCT)

Drug: Cyclosporine

Drug: Hydrocortisone

Procedure: Total lymphoid irradiation (TLI)

Study type

Interventional

Funder types

Other

Identifiers

NCT00482053

IRB-06703

BMT186 (Other Identifier)

97355 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

3 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

3 participants in 1 patient group

Auto-HCT followed by Allo-HCT for Poor-risk DLBCL

Experimental group

Description:

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.

Treatment: