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

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: NCT00612716
Recruitment Status : Completed
First Posted : February 12, 2008
Last Update Posted : December 18, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE February 9, 2008
First Posted Date  ICMJE February 12, 2008
Last Update Posted Date December 18, 2019
Actual Study Start Date  ICMJE October 6, 1999
Actual Primary Completion Date November 15, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2012)
  • Engraftment failure [ Time Frame: 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.
  • Time to engraftment [ Time Frame: 3 Months ]
    Time to first of 3 consecutive days with absolute neutrophil count (ANC) > 500/:l. Time to platelet transfusion independence (platelets > 20,000 with no transfusions for the following 7 days). Time to red blood cell (RBC) transfusion independence (Hemoglobin > 9.0 with no transfusions for the following 15 days).
  • Incidence and severity of acute graft-versus-host disease [ Time Frame: Day 100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
  • Persistence or relapse of malignancy [ Time Frame: 3 Years ]
    the return of disease after its apparent recovery/cessation.
  • Overall Survival [ Time Frame: Annually ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 9, 2008)
  • Engraftment failure
  • Time to engraftment
  • Incidence and severity of acute and chronic graft-versus-host disease
  • Persistence or relapse of malignancy
  • Survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2012)
Incidence and severity of chronic GVHD. [ Time Frame: 1 Year ]
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
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 Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia
Official Title  ICMJE Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
Intervention  ICMJE
  • 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 Name: 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 Name: 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 Name: TBI
Study Arms  ICMJE 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.
Interventions:
  • Drug: busulfan
  • Drug: cyclophosphamide
  • Biological: Stem cell infusion
  • Radiation: Total body irradiation
Publications * Not Provided

*   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: December 16, 2019)
6
Original Enrollment  ICMJE
 (submitted: February 9, 2008)
70
Actual Study Completion Date  ICMJE December 15, 2019
Actual Primary Completion Date November 15, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 55 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00612716
Other Study ID Numbers  ICMJE 1999LS060
9909M18181 ( Other Identifier: IRB, University of Minnesota )
UMN-MT1999-14 ( Other Identifier: Blood and Marrow Transplantation Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Daniel J. Weisdorf, MD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date December 2019

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