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

December 24, 2019 updated by: Fred Hutchinson Cancer Center

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

63

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Leipzig, Germany, D-04103
        • Universitaet Leipzig
  • Italy
      • Torino, Italy, 10126
        • University of Torino
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Medical Center
      • Stanford, California, United States, 94305
        • Stanford University Hospitals and Clinics
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Radiation: total-body irradiation
Undergo TBI
Other Names:
  • TBI
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Drug: cyclosporine
Given IV or PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Biological: therapeutic allogeneic lymphocytes
Undergo DLI
Other Names:
  • ALLOLYMPH
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: chemotherapy
Undergo cytoreductive chemotherapy
Other Names:
  • chemo
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 5 years
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
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
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.
Up to 5 years
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.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 5 years
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.
Up to day 56
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.
Up to day 90
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.
Up to day 90 post-DLI
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.
Up to day 56
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.
Up to 1 year post-DLI
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.
Up to 5 years
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.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 1997

Primary Completion (ACTUAL)

April 1, 2002

Study Completion (ACTUAL)

April 1, 2002

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 16, 2004

First Posted (ESTIMATE)

July 19, 2004

Study Record Updates

Last Update Posted (ACTUAL)

December 27, 2019

Last Update Submitted That Met QC Criteria

December 24, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1225.00 (OTHER: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
  • P30CA015704 (U.S. NIH Grant/Contract)
  • NCI-2012-00592 (REGISTRY: CTRP (Clinical Trial Reporting Program))
  • #1225.00A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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