Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

Sponsor
Masonic Cancer Center, University of Minnesota (Other)
Overall Status
Completed
CT.gov ID
NCT00612716
Collaborator
(none)
6
Enrollment
1
Location
1
Arm
242.3
Actual Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy, such as cyclophosphamide and busulfan, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells from bone marrow or umbilical cord blood may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving methotrexate and cyclosporine after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

OBJECTIVES:
  • Determine if allogeneic stem cell transplantation using unrelated matched or related haploidentical donor bone marrow or unrelated matched cord blood results in timely, complete, and durable engraftment in patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

  • Determine the incidence and grade of acute and chronic graft-versus-host disease in patients treated with this regimen.

  • Determine if the augmented graft-versus-tumor effect accompanying unrelated or partially matched donor allogeneic transplant reduces the incidence of relapse in these patients.

OUTLINE:
  • Preparative regimen: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6 and undergo total-body irradiation (TBI) twice daily on days -4 to -1. Patients who are unable to undergo TBI receive busulfan IV or orally 4 times daily on days -9 to -6 and cyclophosphamide IV over 2 hours on days -5 to -2.

  • Stem cell transplantation: All patients undergo unrelated matched bone marrow or umbilical cord blood transplantation or partially matched related allogeneic bone marrow transplantation on day 0.

  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis comprising methotrexate and cyclosporine. Patients may be enrolled in other protocols directed towards GVHD prophylaxis.

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
Actual Study Start Date :
Oct 6, 1999
Actual Primary Completion Date :
Nov 15, 2019
Actual Study Completion Date :
Dec 15, 2019

Arms and Interventions

ArmIntervention/Treatment
Experimental: Allogeneic Transplantation

Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.

Drug: busulfan
For those not eligible for total body irradiation: busulfan 4 mg/kg/day orally (1 mg/kg orally every 6 hrs) on Days -9 through -6.
Other Names:
  • Busulfex
  • Drug: cyclophosphamide
    Cyclophosphamide 60 mg/kg/day on days -7 and -6. For patients not eligible for total body irradiation: cytoxan 50 mg/kg intravenously (IV) on days -5 through -2.
    Other Names:
  • Cytoxan
  • Biological: Stem cell infusion
    Infused on Day 0
    Other Names:
  • umbilical cord blood transplantation
  • hematopoietic stem cell transplantation
  • allogeneic transplantation
  • bone marrow transplantation
  • Radiation: Total body irradiation
    165 cGy morning and evening on days -4 through -1.
    Other Names:
  • TBI
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Engraftment Failure [3 Months]

      Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.

    2. Number of Participants With Neutrophil Engraftment [Day 42]

      Time to 1st 3 consecutive days with absolute neutrophil count (ANC) > 5 x 10^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence).

    3. Number of Participants With Platelet Engraftment [Day 180]

      Time to platelets > 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment >50,000 by day 100.

    4. Number of Participants With Grade 3-4 Acute Graft-versus-host Disease [Day 100]

      Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

    5. Number of Participants With Persistence Disease [3 Years]

      the return of disease after its apparent recovery/cessation.

    6. Number of Participants With Relapse of Malignancy [3 Years]

      the return of disease after its apparent recovery/cessation.

    7. Number of Participants With 1 Year Overall Survival [1 year]

      The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.

    8. Number of Participants With 2 Year Overall Survival [2 year]

      The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.

    Secondary Outcome Measures

    1. Number of Participants With of Chronic GVHD. [1 Year]

      Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A to 55 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Donors will be <55 years of age and in good health as approved by the National Marrow Donor Program (NMDP) donor and collection centers. Related donors will be < 70 years of age.

    • Recipients will be <55 years, will have satisfactory organ function (excluding bone marrow) and will have a Karnofsky activity assessment >90% and will have:

    • Creatinine <2.0 mg/dl.

    • Bilirubin, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2 x normal.

    • Pulmonary function test and Carbon Monoxide Diffusing Capacity (DLCO) > 50% of normal.

    • Multi Gated Acquisition Scan (MUGA) >45% injection fraction.

    • Recipients with unrelated donor matched at the HLA A, B, DRBI loci, or if < 35 years mismatched at a single HLA A or B, or DRBI locus.

    • Umbilical cord blood (5) used as an unrelated stem cell source will provide > 2.0 x 10^7 cells/kg and will be matched at 4 - 6 of 6 HLA A, B, and DRBI loci. Cord blood grafts may include a single or pair of cord units depending on the cell dose.

    • Partially matched related donors will be at least haploidentical (matched at >3 of 6 HLA A, B, DRB1 loci).

    • Recipients will fall under one of the following disease categories

    • Chronic lymphocytic leukemia -- must have all three:

    • Rai Stage III/IV

    • Progression after previous Complete Response (CR) or Partial Response (PR) including purine antagonist (i.e. fludarabine).

    • Recent chemotherapy responsiveness

    • Advanced non-Hodgkin's lymphoma(NHL).

    • Low-grade NHL (Working Formulation A, B, C) following progression after initial therapy if asymptomatic at diagnosis (>CR2, >PR2; response duration < 1 year from last therapy) or if no CR was achieved (>PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).

    • Mantle zone lymphoma after any progression following initial therapy (>CR1,

    PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).

    • Intermediate grade lymphoma (>PR2). Response duration <1 year from prior therapy.

    • High-grade Non-Hodgkin's Lymphoma (NHL) (IWF H, I, J) after initial therapy if >stage III at diagnosis; after any progression even if localized (stage I, II) at diagnosis with prior response duration < 1 year.

    • Recent chemotherapy responsiveness after treatment with > 3 intermediate intensity regimens.

    • Advanced Hodgkin's disease beyond PR2 (>CR3, >PR3).

    • Recent chemotherapy responsiveness

    • Multiple Myeloma (>CR2, >PR2) or after initial therapy if no prior PR.

    • Recent chemotherapy responsiveness

    • Recipients will sign informed consent approved by the Committee on the Use of Human Subjects at the University of Minnesota.

    Exclusion Criteria:
    • No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Masonic Cancer Center, University of MinnesotaMinneapolisMinnesotaUnited States55455

    Sponsors and Collaborators

    • Masonic Cancer Center, University of Minnesota

    Investigators

    • Principal Investigator: Daniel J. Weisdorf, MD, Masonic Cancer Center, University of Minnesota

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00612716
    Other Study ID Numbers:
    • 1999LS060
    • 9909M18181
    • UMN-MT1999-14
    First Posted:
    Feb 12, 2008
    Last Update Posted:
    Dec 9, 2020
    Last Verified:
    Nov 1, 2020
    Keywords provided by Masonic Cancer Center, University of Minnesota
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Period Title: Overall Study
    STARTED6
    COMPLETED6
    NOT COMPLETED0

    Baseline Characteristics

    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Overall Participants6
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    6
    100%
    >=65 years
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    3
    50%
    Male
    3
    50%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    1
    16.7%
    Unknown or Not Reported
    5
    83.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    5
    83.3%
    More than one race
    0
    0%
    Unknown or Not Reported
    1
    16.7%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants With Engraftment Failure
    DescriptionGraft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
    Time Frame3 Months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    1
    16.7%
    2. Primary Outcome
    TitleNumber of Participants With Neutrophil Engraftment
    DescriptionTime to 1st 3 consecutive days with absolute neutrophil count (ANC) > 5 x 10^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence).
    Time FrameDay 42

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    5
    83.3%
    3. Primary Outcome
    TitleNumber of Participants With Platelet Engraftment
    DescriptionTime to platelets > 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment >50,000 by day 100.
    Time FrameDay 180

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    2
    33.3%
    4. Primary Outcome
    TitleNumber of Participants With Grade 3-4 Acute Graft-versus-host Disease
    DescriptionAcute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
    Time FrameDay 100

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    3
    50%
    5. Primary Outcome
    TitleNumber of Participants With Persistence Disease
    Descriptionthe return of disease after its apparent recovery/cessation.
    Time Frame3 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    1
    16.7%
    6. Primary Outcome
    TitleNumber of Participants With Relapse of Malignancy
    Descriptionthe return of disease after its apparent recovery/cessation.
    Time Frame3 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    1
    16.7%
    7. Primary Outcome
    TitleNumber of Participants With 1 Year Overall Survival
    DescriptionThe percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.
    Time Frame1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    2
    33.3%
    8. Primary Outcome
    TitleNumber of Participants With 2 Year Overall Survival
    DescriptionThe percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.
    Time Frame2 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    1
    16.7%
    9. Secondary Outcome
    TitleNumber of Participants With of Chronic GVHD.
    DescriptionChronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
    Time Frame1 Year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    Measure Participants6
    Count of Participants [Participants]
    0
    0%

    Adverse Events

    Time Frame5 years
    Adverse Event Reporting Description
    Arm/Group TitleAllogeneic Transplantation
    Arm/Group DescriptionPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
    All Cause Mortality
    Allogeneic Transplantation
    Affected / at Risk (%)# Events
    Total6/6 (100%)
    Serious Adverse Events
    Allogeneic Transplantation
    Affected / at Risk (%)# Events
    Total3/6 (50%)
    Injury, poisoning and procedural complications
    Primary graft failure1/6 (16.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Death3/6 (50%) 3
    Other (Not Including Serious) Adverse Events
    Allogeneic Transplantation
    Affected / at Risk (%)# Events
    Total6/6 (100%)
    Blood and lymphatic system disorders
    Platelet refractory1/6 (16.7%) 1
    Anemia1/6 (16.7%) 1
    Disseminated Intravascular Coagulation1/6 (16.7%) 1
    Duodenal capillary congestion1/6 (16.7%) 1
    Hemolysis4/6 (66.7%) 5
    Subarachoid bleed1/6 (16.7%) 1
    Thrombosis1/6 (16.7%) 2
    Uremic platelet dysfunction1/6 (16.7%) 2
    Vascular disorder, other1/6 (16.7%) 1
    Veno occulisive disease1/6 (16.7%) 1
    Cardiac disorders
    Cardiac disorder, other1/6 (16.7%) 1
    Pancytopenic1/6 (16.7%) 1
    Pericardial effusion1/6 (16.7%) 1
    Gastrointestinal disorders
    GI bleeding4/6 (66.7%) 5
    Immune system disorders
    Graft vs host disease1/6 (16.7%) 1
    Infections and infestations
    Abnormal bilirubin3/6 (50%) 6
    Infection5/6 (83.3%) 80
    Pneumonia3/6 (50%) 5
    Sepsis1/6 (16.7%) 1
    Septicemia1/6 (16.7%) 1
    Investigations
    Elevated Partial Thromboplastin Time1/6 (16.7%) 1
    Hypokalemic1/6 (16.7%) 1
    Hypomagnesmia1/6 (16.7%) 1
    Metabolism and nutrition disorders
    Failure to thrive1/6 (16.7%) 1
    Musculoskeletal and connective tissue disorders
    muscle disorder other1/6 (16.7%) 1
    Myopathy1/6 (16.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Active Malignancy5/6 (83.3%) 6
    Nervous system disorders
    Epileptic episode1/6 (16.7%) 1
    Learning Dysfunction1/6 (16.7%) 1
    Neurotoxicity2/6 (33.3%) 2
    Seizure1/6 (16.7%) 1
    Renal and urinary disorders
    Cyclosporine renal dysfunction2/6 (33.3%) 2
    Dialysis3/6 (50%) 3
    Embolization of uterine artery1/6 (16.7%) 1
    Hemolytic uremia1/6 (16.7%) 1
    Increased creatinine2/6 (33.3%) 2
    Renal failure4/6 (66.7%) 4
    Reproductive system and breast disorders
    Acute sinusitis1/6 (16.7%) 1
    Hypogonadism2/6 (33.3%) 2
    Vaginal bleeding1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndorme2/6 (33.3%) 2
    Intubation4/6 (66.7%) 4
    Skin and subcutaneous tissue disorders
    Drug toxicity2/6 (33.3%) 2
    Vascular disorders
    Hypertension4/6 (66.7%) 4

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDr. Daniel J.Weisdorf, M.D
    OrganizationMasonic Cancer Center, University of Minnesota
    Phone612 624-3101
    Emailweisd001@umn.edu
    Responsible Party:
    Masonic Cancer Center, University of Minnesota
    ClinicalTrials.gov Identifier:
    NCT00612716
    Other Study ID Numbers:
    • 1999LS060
    • 9909M18181
    • UMN-MT1999-14
    First Posted:
    Feb 12, 2008
    Last Update Posted:
    Dec 9, 2020
    Last Verified:
    Nov 1, 2020