Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed By Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00003196
First received: November 1, 1999
Last updated: April 25, 2014
Last verified: April 2014

November 1, 1999
April 25, 2014
September 1997
April 2002   (final data collection date for primary outcome measure)
  • Incidence of GVHD, myelosuppression, and infections [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    At the conclusion of the study, all unexpected toxicities will be summarized and reported.
  • Greater than 10% incidence of treatment-related mortality (TRM) after PBSC infusion, defined as death without evidence of disease progression [ Time Frame: Within 65 days of transplant ] [ Designated as safety issue: Yes ]
  • Greater than 20% incidence of TRM after DLI, defined as death without evidence of disease progression [ Time Frame: Within 12 months of DLI ] [ Designated as safety issue: Yes ]
  • Proportion of patients who successfully achieve mixed chimerism [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The proportion of patients who successfully establish mixed chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.
  • Proportion of patients with mixed chimerism who successfully achieve full donor chimerism [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The proportion of patients with mixed chimerism who are successfully converted to full donor chimerism in each group (patients with NHL, CLL or multiple myeloma vs patients with other malignancies) will be estimated and corresponding confidence intervals will be presented.
Not Provided
Complete list of historical versions of study NCT00003196 on ClinicalTrials.gov Archive Site
  • Response of malignancy to DLI [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Incidence of myelosuppression after initial PBSC transplant [ Time Frame: Up to day 56 ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Incidence of aplasia after DLI [ Time Frame: Up to day 90 ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Incidence of grades 2-4 acute GVHD after DLI [ Time Frame: Up to day 90 post-DLI ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Incidence of grades 2-4 acute GVHD after PBSC infusion [ Time Frame: Up to day 56 ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Incidence of chronic extensive GVHD after DLI [ Time Frame: Up to 1 year post-DLI ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Dose of cluster of differentiation (CD)3+ cells required to convert mixed to full lymphoid chimeras [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
  • Incidence of non-relapse mortality [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Not Provided
Not Provided
Not Provided
 
Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed By Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
Induction Of Mixed Hematopoietic Chimerism In Older Patients With B-Cell Malignancies and in Selected Other Diseases, Using Low Dose TBI , PBSC Infusion And Post-Transplant Immunosuppression With Cyclosporine And Mycophenolate Mofetil to be Followed by Donor Lymphocyte Infusion: A Pilot Study.

It is known that immune reactions of the donor cells against cancer contribute significantly to the ability to achieve cure after bone marrow transplant (BMT). This research study will test an approach to treating cancer that uses immune cells from the donor to fight the cancer cells. The main reason for using this treatment is the evidence that strong immune responses can occur from donor cells and remissions from cancer have been reported in patients whose cancer came back after a bone marrow transplant. This type of treatment is called a donor leukocyte infusion or DLI. It has been shown that it is possible to get complete remissions of the cancer by using DLI. Most success with the use of DLI has been in a form of leukemia called chronic myeloid leukemia. However, there is good evidence that this effect can occur in other diseases including multiple myeloma, lymphoma, and chronic lymphocytic leukemia. This type of immune response against cancer cells is usually called a graft-versus-leukemia (GVL) effect

PRIMARY OBJECTIVES:

I. To determine whether mixed hematopoietic chimerism can be safely established using a non-myeloablative conditioning regimen in patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma.

II. To determine whether mixed chimerism, established with non- myeloablative conditioning regimens, can be safely converted to full donor hematopoietic chimerism by infusions of donor lymphocytes (DLI).

OUTLINE:

CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators.

CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic peripheral blood stem cell (PBSC) transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine intravenously (IV) twice daily (BID) on days -1 to 0 and then orally (PO) BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of graft-vs-host disease (GVHD) undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period.

After completion of study treatment, patients are followed up at 4, 6, 12, 18, and 24 months and then annually thereafter.

Interventional
Not Provided
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-cell Leukemia/Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Refractory Multiple Myeloma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Drug: chemotherapy
    Undergo cytoreductive chemotherapy
    Other Name: chemo
  • Radiation: total-body irradiation
    Undergo TBI
    Other Name: TBI
  • Procedure: peripheral blood stem cell transplantation
    Undergo allogeneic PBSC transplant
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Drug: cyclosporine
    Given IV or PO
    Other Names:
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Drug: mycophenolate mofetil
    Given PO
    Other Names:
    • Cellcept
    • MMF
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Undergo allogeneic PBSC transplant
  • Biological: therapeutic allogeneic lymphocytes
    Undergo DLI
    Other Name: ALLOLYMPH
Experimental: Treatment (irradiation, transplant, immunosuppression, DLI)

CYTOREDUCTION: If necessary, patients with advanced malignancies undergo cytoreductive chemotherapy to reduce tumor size at discretion of primary physician and study investigators.

CONDITIONING REGIMEN: Patients undergo low-dose total-body irradiation followed by allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine IV BID on days -1 to 0 and then PO BID on days 1-35 with taper to day 56. Patients also receive mycophenolate mofetil PO BID on days 0-27.

POST-TRANSPLANT DLI: Patients with mixed chimerism on day 56 and no evidence of GVHD undergo DLI over 30 minutes on day 65 and may receive up to 3 additional infusions in the absence of GVHD and disease progression or persistence. Patients who have not achieved mixed chimerism at day 56 undergo DLI if complete response is not obtained after a 2 month monitoring period.

Interventions:
  • Drug: chemotherapy
  • Radiation: total-body irradiation
  • Procedure: peripheral blood stem cell transplantation
  • Drug: cyclosporine
  • Drug: mycophenolate mofetil
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Biological: therapeutic allogeneic lymphocytes
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
Not Provided
April 2002   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients aged > 49 years and < 66 years with NHL, CLL and multiple myeloma who are not eligible for autologous transplantation or have failed prior autologous transplantation; patients with NHL and CLL must have failed prior therapy with an alkylating agent and/or fludarabine; patients with multiple myeloma must have stage II or III disease and received prior chemotherapy
  • Patients < 50 years of age with NHL, CLL and multiple myeloma at high risk of regimen related toxicity through prior autologous transplant or through pre-existing chronic disease affecting kidneys, liver, lungs, and heart will be considered on a case by case basis and presented to professional clinical counselor (PCC)
  • Patients < 66 years of age with other diseases treatable by allogeneic BMT whom through pre-existing chronic disease affecting kidneys, liver, lungs, and heart are considered to be at high risk for regimen related toxicity using standard high dose regimens; autografting must also be contraindicated in these patients and they must be approved for this protocol by both PCC and by the principle investigator; the following diseases are the likely candidates but other less common diseases may be considered and approved by PCC:

    • Myelodysplastic syndromes
    • Myeloproliferative syndromes
    • Acute leukemia in remission
    • Chronic myelogenous leukemia (CML) in 2nd chronic phase
    • Hodgkin's disease
  • Selected patients with any of the above diagnosis who are (a) older than 65 years and < 75 years with a Karnofsky score > 70 and who, apart from age, fulfill eligibility criteria, or (b) < 66 years but ineligible solely because of renal dysfunction; these patients must be approved for transplant by both PCC and the principal investigator
  • DONOR: Human leukocyte antigen (HLA) genotypically identical sibling
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)
  • DONOR: Age < 75

Exclusion Criteria:

  • Eligible for autologous transplantation
  • Patients with rapidly progressive high grade NHL
  • History of central nervous system (CNS) involvement with disease
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant
  • Patients with a creatinine clearance < 50 ml/min
  • Cardiac ejection fraction < 40% or cardiac failure requiring therapy
  • Severe defects in pulmonary function testing (defects are currently categorized as mild, moderate and severe) as defined by the pulmonary consultant, or receiving supplementary continuous oxygen
  • Total bilirubin > 2 x the upper limit of normal
  • Serum glutamic pyruvate transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) 4 x the upper limit of normal
  • Karnofsky score < 50
  • Patients with poorly controlled hypertension
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with human immunodeficiency virus (HIV)
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
  • DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for donation as described in the Standard Practice Guidelines
Both
50 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Germany,   Italy
 
NCT00003196
1225.00, NCI-2012-00592
Not Provided
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP