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

November 12, 2020 updated by: Masonic Cancer Center, University of Minnesota

Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

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

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota

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

No older than 55 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: 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:
  • hematopoietic stem cell transplantation
  • bone marrow transplantation
  • umbilical cord blood transplantation
  • allogeneic transplantation
Radiation: Total body irradiation
165 cGy morning and evening on days -4 through -1.
Other Names:
  • TBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Neutrophil Engraftment
Time Frame: 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).
Day 42
Number of Participants With Platelet Engraftment
Time Frame: 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.
Day 180
Number of Participants With 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.
3 Months
Number of Participants With Grade 3-4 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.
Day 100
Number of Participants With Persistence Disease
Time Frame: 3 Years
the return of disease after its apparent recovery/cessation.
3 Years
Number of Participants With Relapse of Malignancy
Time Frame: 3 Years
the return of disease after its apparent recovery/cessation.
3 Years
Number of Participants With 1 Year Overall Survival
Time Frame: 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.
1 year
Number of Participants With 2 Year Overall Survival
Time Frame: 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.
2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With 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.
1 Year

Collaborators and Investigators

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

Sponsor

Masonic Cancer Center, University of Minnesota

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)

October 6, 1999

Primary Completion (ACTUAL)

November 15, 2019

Study Completion (ACTUAL)

December 15, 2019

Study Registration Dates

First Submitted

February 9, 2008

First Submitted That Met QC Criteria

February 9, 2008

First Posted (ESTIMATE)

February 12, 2008

Study Record Updates

Last Update Posted (ACTUAL)

December 9, 2020

Last Update Submitted That Met QC Criteria

November 12, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1999LS060
  • 9909M18181 (OTHER: IRB, University of Minnesota)
  • UMN-MT1999-14 (OTHER: Blood and Marrow Transplantation Program)

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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