Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00003196
Recruitment Status : Completed
First Posted : July 19, 2004
Last Update Posted : December 27, 2019
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE November 1, 1999
First Posted Date  ICMJE July 19, 2004
Last Update Posted Date December 27, 2019
Actual Study Start Date  ICMJE September 1997
Actual Primary Completion Date April 2002   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2012)
  • Incidence of GVHD, myelosuppression, and infections [ Time Frame: Up to 5 years ]
    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 ]
  • Greater than 20% incidence of TRM after DLI, defined as death without evidence of disease progression [ Time Frame: Within 12 months of DLI ]
  • Proportion of patients who successfully achieve mixed chimerism [ Time Frame: Up to 5 years ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 30, 2014)
  • Response of malignancy to DLI [ Time Frame: Up to 5 years ]
    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 ]
    Defined as (absolute neutrophil count [ANC] < 500 for > 2 days, platelets < 20,000 for > 2 days). 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Examined separately in the two groups of patients, and reported in a descriptive manner with confidence intervals presented.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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.
Brief Summary This pilot clinical trial studies low-dose total body irradiation and donor peripheral blood stem cell transplant followed by donor lymphocyte infusion in treatment patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma. Giving total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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 Acute Lymphoblastic Leukemia
  • 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
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Publications * Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Petersen SL, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hübel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg HJ, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2020 Jun 4. doi: 10.3324/haematol.2020.248187. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 30, 2014)
63
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2002
Actual Primary Completion Date April 2002   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 bone marrow transplant (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 principal 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 glutamate 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00003196
Other Study ID Numbers  ICMJE 1225.00
NCI-2012-00592 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
#1225.00A
1225.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date December 2019

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