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

Fred Hutchinson Cancer Center (FHCC) logo

Fred Hutchinson Cancer Center (FHCC)

Status

Completed

Conditions

Cutaneous B-cell Non-Hodgkin Lymphoma
Refractory Multiple Myeloma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Splenic Marginal Zone Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Anaplastic Large Cell Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Diffuse Mixed Cell Lymphoma
Small Intestine Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Testicular Lymphoma
Refractory Chronic Lymphocytic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Angioimmunoblastic T-cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Intraocular Lymphoma
Noncutaneous Extranodal Lymphoma
Waldenström Macroglobulinemia
Recurrent Small Lymphocytic Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Stage III Multiple Myeloma
Hepatosplenic T-cell Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Refractory Hairy Cell Leukemia
Peripheral T-cell Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Stage II Multiple Myeloma

Treatments

Radiation: total-body irradiation
Biological: therapeutic allogeneic lymphocytes
Drug: mycophenolate mofetil
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Drug: cyclosporine
Drug: chemotherapy

Study type

Interventional

Funder types

Other
NIH

Identifiers

NCT00003196
#1225.00A
1225.00 (Other Identifier)
P30CA015704 (U.S. NIH Grant/Contract)
NCI-2012-00592 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

63 patients

Sex

All

Ages

50 to 65 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

63 participants in 1 patient group

Treatment (irradiation, transplant, immunosuppression, DLI)
Experimental group
Description:
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.
Treatment:
Drug: cyclosporine
Drug: chemotherapy
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: mycophenolate mofetil
Biological: therapeutic allogeneic lymphocytes
Radiation: total-body irradiation

Trial contacts and locations

5

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Data sourced from clinicaltrials.gov

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