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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00612716
First received: February 9, 2008
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Drug: busulfan
Drug: cyclophosphamide
Biological: Stem cell infusion
Radiation: Total body irradiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Engraftment failure [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    the return of disease after its apparent recovery/cessation.

  • Overall Survival [ Time Frame: Annually ] [ Designated as safety issue: No ]

    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:
  • Incidence and severity of chronic GVHD. [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.


Estimated Enrollment: 15
Study Start Date: October 1999
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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

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.
  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612716

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Daniel J. Weisdorf, MD    612-624-0123    weisd001@umn.edu   
Principal Investigator: Daniel Weisdorf, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Daniel J. Weisdorf, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00612716     History of Changes
Other Study ID Numbers: 1999LS060, 9909M18181, UMN-MT1999-14
Study First Received: February 9, 2008
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
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

Additional relevant MeSH terms:
Neoplasms
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Busulfan
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on July 26, 2014