Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia
This study is currently recruiting participants.
Verified February 2013 by Masonic Cancer Center, University of Minnesota
Sponsor:
Masonic Cancer Center, University of Minnesota
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00612716
First received: February 9, 2008
Last updated: February 5, 2013
Last verified: February 2013
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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:
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
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: | February 5, 2013 |
| 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 May 16, 2013