Chronic Myeloproliferative DisordersNCT00453206
Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Diseases
A study testing allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Chronic Myeloproliferative Disorders and Leukemia, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and melphalan, before a donor peripheral stem cell transplant or bone marrow transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages Up to 70 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation and nonmyeloablative allogeneic hematopoietic stem cell transplantation
- Type of treatment
- Surgery or procedure
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Aug 2014
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed hematological disease, including any of the following:
- Chronic lymphocytic leukemia
- Absolute lymphocytosis > 5,000/µL
- Morphologically mature lymphocytes with < 55% prolymphocytes
- Lymphocyte phenotype with expression of CD19 and CD5
- Absence of CD23 expression allowed provided disease is morphologically distinguished from mantle cell lymphoma
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- Prolymphocytic leukemia
- Absolute lymphocytosis > 5,000/µL
- Morphologically mature lymphocytes with > 55% prolymphocytes
- Non-Hodgkin's or Hodgkin's lymphoma
- Any WHO classification histologic subtype
- Diagnosis by core biopsy allowed provided there is adequate tissue for diagnosis and immunophenotyping
- Diagnosis by bone marrow biopsy not acceptable for follicular lymphomas
- Multiple myeloma
- Has received ≥ 1 prior treatment regimen
- Has a partial response or greater by the Blade Criteria
- Patients who achieved complete remission are eligible
- Acute myeloid leukemia
- Documented control (i.e., < 10% bone marrow blasts and no circulating blasts)
- Myelodysplastic syndromes
- Documented disease as defined by WHO or French-American-British Cooperative group criteria
- Chronic myelogenous leukemia
- Patients with atypical chronic myelogenous leukemia (i.e., absent Philadelphia chromosome) are eligible
- Polycythemia vera
- Documented disease as defined by WHO criteria (i.e., A1 + A2, and any other category A, OR A1 + A2, and any 2 category B):
- A1: Total red blood cell mass > 25% above mean normal predicted value OR hemoglobin > 18.5 g/dL in males, 16.5 g/dL in females (hematocrit ≥ 60% in males or ≥ 56% in females)
- A2: No cause of secondary erythrocytosis (absence of familial erythrocytosis, no elevation of epoetin alfa [EPO] due to hypoxia, high oxygen affinity hemoglobin, truncated EPO receptor, or inappropriate ectopic EPO production)
- A3: Splenomegaly
- A4: Clonal genetic abnormality other than the Philadelphia chromosome
- A5: Endogenous erythroid colony formation in vitro
- B: Platelet count > 400,000/mm³, WBC > 12,000/mm³, bone marrow biopsy with prominent erythroid and megakaryocytic proliferation, and low serum EPO
- Chronic idiopathic myelofibrosis
- Documented disease as defined by WHO criteria
- Must have a HLA-identical donor, a matched unrelated donor, or a HLA 9/10 related donor meeting the following criteria:
- HLA-identical sibling (6/6)
- Serologic typing for class I (A, B)
- Molecular typing for class II (DRB1)
- 9/10 matched related donor
- High-resolution molecular typing at HLA-A, B, C, DRB1, and DQB1
- Only a single mismatch at one class I or II allele allowed
- 10/10 matched unrelated donor
- Molecular identity at HLA-A, B, C, DRB1, and DQB1 by high-resolution typing
- Syngeneic donors are not eligible
- Creatinine clearance ≥ 40 mL/min
- Bilirubin ≤ 3 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- DLCO ≥ 40% with no symptomatic pulmonary disease
- LVEF ≥ 30% by cardiac MRI or echocardiogram with no symptomatic cardiac disease
- Fertile patients willing to use effective contraception
Who cannot join
- Uncontrolled diabetes mellitus
- Active serious infection
- Known hypersensitivity to E. coli-derived products
- Known HIV positivity
- History of another malignancy*, meeting the following criteria:
- Non-skin malignancy or melanoma within the past 5 years
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- Concomitant malignancy that has not been curatively treated
- NOTE: *However, cancer survivors who have undergone potentially curative therapy for a prior malignancy at least 5 years before enrollment and are deemed at low risk of < 30% for recurrence by their treating physicians is considered
- Pregnant or nursing
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
About this study
Official title: Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases
RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and melphalan, before a donor peripheral stem cell transplant or bone marrow transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, mycophenolate mofetil, and antithymocyte globulin before and after transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer or abnormal cells as not belonging in the patient's body and destroy them (graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with hematologic cancer or other diseases.
Read the detailed description
OBJECTIVES:
Primary
- Determine the feasibility (i.e., risk of treatment-related mortality during the first 6 months after transplantation) of administering reduced-intensity allogeneic hematopoietic stem cell transplantation to patients with hematologic cancer or other diseases.
Secondary
- Determine the response rate (partial and complete response), 6- and 12-month probabilities of response, and time to progression in patients treated with this regimen.
- Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine other toxicities of this regimen in these patients.
- Determine the overall survival and disease-free survival of patients treated with this regimen.
- Determine the impact of iron status on overall and disease-free survival.
- Determine the influence of quality of life (at time of transplantation) on overall survival.
OUTLINE:
- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and -3 or melphalan IV over 2 hours on day -3.
- Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days -1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1.
- Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover.
- Lymphocyte infusion: Patients with progressive or stable disease while off immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions from the original donor at 8-week intervals beginning on day 180 or 210 .
Quality of life is assessed at baseline.
After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Being tested
- allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation, nonmyeloablative allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), accelerated phase chronic myelogenous leukemia, adult acute myeloid leukemia in remission, blastic phase chronic myelogenous leukemia, primary myelofibrosis, chronic phase chronic myelogenous leukemia, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, de novo myelodysplastic syndromes, nodal marginal zone B-cell lymphoma, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Accelerated Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allogeneic bone marrow transplantationProcedure or surgery
allogeneic hematopoietic stem cell transplantationProcedure or surgery
nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery
peripheral blood stem cell transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related Mortality Within the First 6 Months After Transplantation
Measured: 6 months
Secondary outcomes (7)
Complete Response
Measured: monthly
Overall Survival
Measured: monthly
Disease-free Survival
Measured: monthly
Graft-versus-host Disease
Measured: monthly
Iron Status at the Time of Transplantation
Measured: baseline
Quality of Life at the Time of Transplantation
Measured: baseline
Treatment-related Mortality at 100 Days After Transplantation
Measured: 100 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2007 (estimated)
- Study startFeb 2007
- Primary completionFeb 2014
- Study completionAug 2014
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 Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Hurd, MD, Study chair, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00453206
- Sponsor's protocol ID
- IRB00001366
- Other IDs
- CCCWFU-29506, IRB00001366
- Status last verified
- Aug 2018
- First submitted
- 27 Mar 2007
- Last updated
- 10 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Allogeneic Hematopoietic Cell Transplantation for Patients With Hematological Diseases
- ClinicalTrials.gov ID
- NCT00453206
- Acronym / sponsor ID
- IRB00001366
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
- Keywords
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), accelerated phase chronic myelogenous leukemia, adult acute myeloid leukemia in remission, blastic phase chronic myelogenous leukemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Feb 2007
- Primary completion
- Feb 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 28 Mar 2007 (estimated)
- Results
- Posted 2 Jul 2014
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 fludarabine, busulfan, and melphalan, before a donor peripheral stem cell transplant or bone marrow transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus, methotrexate, mycophenolate mofetil, and antithymocyte globulin before and after transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer or abnormal cells as not belonging in the patient's body and destroy them (graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with hematologic cancer or other diseases.
Detailed description
OBJECTIVES:
Primary
- Determine the feasibility (i.e., risk of treatment-related mortality during the first 6 months after transplantation) of administering reduced-intensity allogeneic hematopoietic stem cell transplantation to patients with hematologic cancer or other diseases.
Secondary
- Determine the response rate (partial and complete response), 6- and 12-month probabilities of response, and time to progression in patients treated with this regimen.
- Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine other toxicities of this regimen in these patients.
- Determine the overall survival and disease-free survival of patients treated with this regimen.
- Determine the impact of iron status on overall and disease-free survival.
- Determine the influence of quality of life (at time of transplantation) on overall survival.
OUTLINE:
- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3. Patients also receive busulfan IV over 2 hours every 6 hours on days -4 and -3 or melphalan IV over 2 hours on day -3.
- Graft-versus-host disease (GVHD) prophylaxis: Patients with matched related donors receive oral tacrolimus twice daily on days -1 to 90 followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6. Patients with matched unrelated and 9/10 matched related donors receive oral tacrolimus twice daily on days -1 to 180 followed by a taper; methotrexate IV on days 1, 3, 6, and 11; and oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper. All patients also receive antithymocyte globulin IV over 4 to 6 hours once a day on days -4 to -1.
- Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) beginning on day 7 and continuing until blood counts recover.
- Lymphocyte infusion: Patients with progressive or stable disease while off immunosuppression and no active GVHD may receive up to 3 donor lymphocyte infusions from the original donor at 8-week intervals beginning on day 180 or 210 .
Quality of life is assessed at baseline.
After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years.
PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (49 listed)
- Histologically confirmed hematological disease, including any of the following:
- Creatinine clearance ≥ 40 mL/min
- Bilirubin ≤ 3 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- DLCO ≥ 40% with no symptomatic pulmonary disease
Key exclusion criteria (9 listed)
- Uncontrolled diabetes mellitus
- Active serious infection
- Known hypersensitivity to E. coli-derived products
- Known HIV positivity
- History of another malignancy*, meeting the following criteria:
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 |
|---|---|---|
| allogeneic bone marrow transplantation | Procedure or surgery | – |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | – |
| nonmyeloablative allogeneic hematopoietic stem cell transplantation | Procedure or surgery | – |
| peripheral blood stem cell transplantation | Procedure or surgery | – |
Primary outcome
Treatment-related Mortality Within the First 6 Months After Transplantation
Time frame: 6 months
7 secondary outcomes
Complete Response
Time frame: monthly
Overall Survival
Time frame: monthly
Disease-free Survival
Time frame: monthly
Graft-versus-host Disease
Time frame: monthly
Iron Status at the Time of Transplantation
Time frame: baseline
Quality of Life at the Time of Transplantation
Time frame: baseline
Treatment-related Mortality at 100 Days After Transplantation
Time frame: 100 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- 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.
David Hurd, MD study chair
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Chronic Myeloproliferative Disorders and Leukemia, run by Wake Forest University Health Sciences 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 49 inclusion and 9 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 10 Sep 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2014). 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?
Treatment-related Mortality Within the First 6 Months After Transplantation (time frame: 6 months). 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 10 Sep 2018; AzTrials last refreshed its copy on 7 Nov 2026.