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

Primary Purpose

Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
busulfan
cyclophosphamide
Stem cell infusion
Total body irradiation
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, Waldenstrom macroglobulinemia, recurrent adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage II adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage II adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, stage I adult lymphoblastic lymphoma, stage II adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent childhood anaplastic large cell lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood nasal type extranodal NK/T-cell lymphoma, Burkitt lymphoma, recurrent childhood small noncleaved cell lymphoma, stage I childhood small noncleaved cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood small noncleaved cell lymphoma

Eligibility Criteria

undefined - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic Transplantation

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Participants With Engraftment Failure
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.
Number of Participants With Neutrophil Engraftment
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).
Number of Participants With Platelet Engraftment
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.
Number of Participants With Grade 3-4 Acute Graft-versus-host Disease
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Number of Participants With Persistence Disease
the return of disease after its apparent recovery/cessation.
Number of Participants With Relapse of Malignancy
the return of disease after its apparent recovery/cessation.
Number of Participants With 1 Year Overall Survival
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.
Number of Participants With 2 Year Overall Survival
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

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

Full Information

First Posted
February 9, 2008
Last Updated
November 12, 2020
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00612716
Brief Title
Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia
Official Title
Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
October 6, 1999 (Actual)
Primary Completion Date
November 15, 2019 (Actual)
Study Completion Date
December 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, Waldenstrom macroglobulinemia, recurrent adult Burkitt lymphoma, stage I adult Burkitt lymphoma, stage II adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage II adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, stage I adult lymphoblastic lymphoma, stage II adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent childhood anaplastic large cell lymphoma, recurrent childhood grade III lymphomatoid granulomatosis, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood nasal type extranodal NK/T-cell lymphoma, Burkitt lymphoma, recurrent childhood small noncleaved cell lymphoma, stage I childhood small noncleaved cell lymphoma, stage II childhood small noncleaved cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood small noncleaved cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Transplantation
Arm Type
Experimental
Arm Description
Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
Busulfex
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Stem cell infusion
Other Intervention Name(s)
umbilical cord blood transplantation, hematopoietic stem cell transplantation, allogeneic transplantation, bone marrow transplantation
Intervention Description
Infused on Day 0
Intervention Type
Radiation
Intervention Name(s)
Total body irradiation
Other Intervention Name(s)
TBI
Intervention Description
165 cGy morning and evening on days -4 through -1.
Primary Outcome Measure Information:
Title
Number of Participants With Engraftment Failure
Description
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 Frame
3 Months
Title
Number of Participants With Neutrophil Engraftment
Description
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).
Time Frame
Day 42
Title
Number of Participants With Platelet Engraftment
Description
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.
Time Frame
Day 180
Title
Number of Participants With Grade 3-4 Acute Graft-versus-host Disease
Description
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame
Day 100
Title
Number of Participants With Persistence Disease
Description
the return of disease after its apparent recovery/cessation.
Time Frame
3 Years
Title
Number of Participants With Relapse of Malignancy
Description
the return of disease after its apparent recovery/cessation.
Time Frame
3 Years
Title
Number of Participants With 1 Year Overall Survival
Description
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.
Time Frame
1 year
Title
Number of Participants With 2 Year Overall Survival
Description
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.
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Number of Participants With of Chronic GVHD.
Description
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame
1 Year

10. Eligibility

Sex
All
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel J. Weisdorf, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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