LeukemiaPhase 2NCT00612716
Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia
A Phase 2 study testing busulfan, cyclophosphamide and Stem cell infusion in people with Leukemia and Lymphoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- busulfan, cyclophosphamide and Stem cell infusion
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Oct 1999to 15 Dec 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 25Show fewer
- 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.
Who cannot join
- No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: 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.
Read the 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.
- Being tested
- busulfan, cyclophosphamide, Stem cell infusion, Total body irradiation
- 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
- Medical subject headings
- Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Hodgkin Disease, Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Extranodal NK-T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
busulfanDrug
Also called Busulfex
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.
cyclophosphamideDrug
Also called Cytoxan
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.
Stem cell infusionBiological
Also called umbilical cord blood transplantation, hematopoietic stem cell transplantation, allogeneic transplantation, bone marrow transplantation
Infused on Day 0
Total body irradiationRadiation
Also called TBI
165 cGy morning and evening on days -4 through -1.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Transplantation | Experimental | Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide. Receives: Drug: busulfan; Drug: cyclophosphamide; Biological: Stem cell infusion; Radiation: Total body irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 Months
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).
Measured: Day 42
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.
Measured: Day 180
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.
Measured: Day 100
Number of Participants With Persistence Disease
the return of disease after its apparent recovery/cessation.
Measured: 3 Years
Number of Participants With Relapse of Malignancy
the return of disease after its apparent recovery/cessation.
Measured: 3 Years
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.
Measured: 1 year
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.
Measured: 2 year
Secondary outcomes (1)
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.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study start6 Oct 1999
- Primary completion15 Nov 2019
- Study completion15 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel J. Weisdorf, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612716
- Sponsor's protocol ID
- 1999LS060
- Other IDs
- 9909M18181, UMN-MT1999-14
- Status last verified
- Nov 2020
- First submitted
- 9 Feb 2008
- Last updated
- 9 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00612716
- Acronym / sponsor ID
- 1999LS060
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- 6 Oct 1999 (actual)
- Primary completion
- 15 Nov 2019 (actual)
- Study completion
- 15 Dec 2019 (actual)
- First posted
- 12 Feb 2008 (estimated)
- Results
- Posted 9 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Transplantation | Experimental | Drug: busulfan, Drug: cyclophosphamide, Biological: Stem cell infusion, Radiation: Total body irradiationPatients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide. |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (25 listed)
- 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:
- 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).
Key exclusion criteria (1 listed)
- No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| busulfanAlso: BusulfexFor 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. | Drug | Allogeneic Transplantation |
| cyclophosphamideAlso: CytoxanCyclophosphamide 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. | Drug | Allogeneic Transplantation |
| Stem cell infusionAlso: umbilical cord blood transplantation, hematopoietic stem cell transplantation, allogeneic transplantation, bone marrow transplantationInfused on Day 0 | Biological | Allogeneic Transplantation |
| Total body irradiationAlso: TBI165 cGy morning and evening on days -4 through -1. | Radiation | Allogeneic Transplantation |
Primary outcome
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.
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).
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.
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.
Number of Participants With Persistence Disease
Time frame: 3 Years
the return of disease after its apparent recovery/cessation.
Number of Participants With Relapse of Malignancy
Time frame: 3 Years
the return of disease after its apparent recovery/cessation.
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.
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.
1 secondary outcome
Number of Participants With of Chronic GVHD.
Time frame: 1 Year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel J. Weisdorf, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing busulfan, cyclophosphamide and Stem cell infusion in people with Leukemia and Lymphoma, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Engraftment Failure (time frame: 3 Months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2020.