Chronic Myeloproliferative DisordersPhase 1/2Bu Flu TBINCT00245037
Busulfan, Fludarabine, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
A Phase 1/2 study testing therapeutic allogeneic lymphocytes, busulfan and cyclosporine in people with Chronic Myeloproliferative Disorders and Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood 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 18 to 80 years
- Conditions the study is for
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
- What is being tested?
- therapeutic allogeneic lymphocytes, busulfan and cyclosporine
- 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
- 147 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Aug 2015
- Phase
- Phase 1/2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of a hematologic malignancy of 1 of the following high-risk types:
- Acute lymphoblastic leukemia
- Acute myeloid leukemia
- Chronic myelogenous leukemia
- Chronic lymphocytic leukemia
- Myelodysplastic syndromes
- Myeloproliferative disorder
- Multiple myeloma
- Plasma cell dyscrasias
- Non-Hodgkin lymphoma
- Hodgkin disease
PATIENT CHARACTERISTICS:
Performance status
- Karnofsky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- No liver failure
- No cirrhosis with evidence of portal hypertension
- No alcoholic hepatitis
- No esophageal varices
- No chronic hepatitis
- No other liver disease
Renal
- Not specified
Cardiovascular
- Left Ventricular Ejection Fraction (LVEF) > 35%
- No symptomatic coronary artery disease or cardiac failure requiring therapy
Pulmonary
- Diffusing capacity of lung for carbon monoxide (DLCO) > 30%
- Total lung capacity > 30%
- Forced expiratory volume in 1 second (FEV_1) > 30%
- No supplementary continuous oxygen
Other
- HIV negative
- No active nonhematologic malignancy except localized skin cancer
- No overt organ dysfunction
PRIOR CONCURRENT THERAPY:
- Not specified
Trial locations and contacts
1 site in 1 country.
United States1 site
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, 97239-3098
About this study
Official title: A Phase I/II Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of Patients With Hematologic Malignancies Using Busulfan, Fludarabine and Total Body Irradiation
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood 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 may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving busulfan and fludarabine together with total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell transplant for hematologic cancer.
Read the detailed description
OBJECTIVES:
Primary
- To assess safety and toxicity of the addition of busulfan added to an established fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for non-myeloablative allogeneic transplantation in patients with hematologic malignancies. (Phase I)
- To assess the non-relapse mortality 1-year after conditioning with busulfan and fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease. (Phase II)
Secondary
- To assess overall survival 1-year survival. (Phase II)
- To assess the incidence of graft rejection. (Phase II)
- To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic extensive GVHD. (Phase II)
- To assess rates of disease progression and/or relapse-related mortality. (Phase II)
- To determine non-hematologic grade III-IV organ specific toxicity. (Phase II)
OUTLINE:
- Nonmyeloablative-conditioning regimen: Patients receive busulfan IV on day -5 and fludarabine IV over 30 minutes on days -4 to -2. Patients undergo total body irradiation on day 0.
- Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo donor PBSC infusion on day 0.
- Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180. Patients with a related stem cell donor receive oral mycophenolate mofetil twice daily on days 0-28. Patients with an unrelated stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed by a taper twice daily to day 56. Patients with evidence of relapse or persistent disease may also receive up to 3 donor lymphocyte infusions.
PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study; 25 patients accrued into the Phase I and 200 patients into Phase II.
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Being tested
- therapeutic allogeneic lymphocytes, busulfan, cyclosporine, fludarabine phosphate, mycophenolate mofetil
- Keywords
- recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, breakpoint cluster region-Abelson (BCR-ABL) negative, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, stage II multiple myeloma, stage III multiple myeloma, primary systemic amyloidosis, refractory multiple myeloma, myelodysplastic/myeloproliferative neoplasm, unclassifiable, chronic eosinophilic leukemia, primary myelofibrosis
- Medical subject headings
- Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Precancerous Conditions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
therapeutic allogeneic lymphocytesBiological
A population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
busulfanDrug
Busulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative.
IV busulfan is available and diluted and administered per package insert guidelines.
cyclosporineDrug
Cyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including Interleukin 2 (IL-2) and Interleukin 4 (IL-4).
- Starting on day -3, Cyclosporine (CSP) is given at a dose of 4.0 mg/kg p.o. b.i.d.
Fludarabine's active metabolite 2-fluoro-ara-A is an antimetabolite that inhibits DNA primase, DNA polymerase alpha and ribonucleotide nuclease.
- Dosing: Days -4, -3 and -2: Fludarabine 30 mg/m2/day IV. Total dose equals 90 mg/m2.
- Monitoring: Fludarabine level is not monitored.
- Dose Adjustments: There are no provisions for fludarabine dose adjustments.
Mycophenolate mofetil (MMF) is the morpholinyl ethyl ester of mycophenolic acid (MPA) and reversibly inhibits inosine monophosphate dehydrogenase, particularly the type II isoform that is more prominent in activated lymphocytes. As a result of the inhibition of de novo purine synthesis, proliferation of B- and T-lymphocytes is blocked and antibody production is inhibited.
- Related Donors: MMF will be given daily at 15mg/kg q 12 hrs until day +28, then stop without tapering. Doses will be rounded to the nearest 250 mg (capsules are 250 mg).
- Unrelated Donors: MMF will be given daily at 15mg/kg q 8 hrs until day +28, then given daily at 15mg/kg q 12 hours until day +56, then stop without tapering. Doses will be rounded to the nearest 250 mg (capsules are 250 mg).
peripheral blood stem cell transplantationProcedure or surgery
Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants:
- In autologous transplants, patients receive their own stem cells.
- In syngeneic transplants, patients receive stem cells from their identical twin.
- In allogeneic transplants, patients receive stem cells from their brother, sister, or parent. A person who is not related to the patient (an unrelated donor) also may be used.
Total Body Irradiation (TBI)Radiation
TBI is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lungs are often partially shielded to lower the risk of radiation-induced lung injury.
- Toxicities: At the dosage used, side effects are not expected. Nevertheless, there may be fever, alopecia, parotitis, diarrhea, reversible skin pigmentation, mucositis and late effects including cataract formation, pulmonary damage, carcinogenesis, and sterilization.
- Dosing: TBI will be given in one 200 cGy fraction from linear accelerator at a rate of 15-19 cGy/min.
Granulocyte colony-stimulating factor (G-CSF)Drug
Granulocyte colony-stimulating factor (G-CSF or GCSF) is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 (CSF 3).
It is a glycoprotein, growth factor and cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to release them into the blood.
- Toxicities: At the dosage used, the most common side effect will be medullary bone pain.
- Dosing: 5 mcg/kg/day given per institutional standards (on approximately days 10-15 or not at all).
PhenytoinDrug
This drug is used to prevent seizures while on chemotherapy.
MethotrexateDrug
Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments.
| Study group | Role | What they receive |
|---|---|---|
| Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) | Experimental | Busulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0 Receives: Biological: therapeutic allogeneic lymphocytes; Drug: busulfan; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation; Radiation: Total Body Irradiation (TBI); Drug: Granulocyte colony-stimulating factor (G-CSF); Drug: Phenytoin; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regimen-Related Toxicities
Non-hematologic toxicities and adverse experiences ≥ Grade 3 occurrences measured up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant. The following data represents the number of regimen-related, grade 3 and 4 toxicities that occurred in each category.
Measured: 5 years post-transplant
Non-relapse Mortality
Percent of subjects with non-relapse mortality two years after conditioning with busulfan with fludarabine/200 cGy TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease.
Measured: Two years post-transplant
Secondary outcomes (5)
Overall Survival
The percentage of overall patient survival (out of 147 participants) for Years 1, 2, 3 and 5.
Measured: Years 1, 2, 3 and 5
Progression-Free Survival
The percentage of progression-free patients (out of 147 participants) at Years 1, 2, 3, and 5.
Definition of Disease Progression:
MM/Plasma Cell: Increasing bone pain or increase in serum/urine monoclonal protein by 25%.
CLL/NHL/HD: New sites of lymphadenopathy; ≥ 25% increase in lymph node size; Blood or bone marrow involvement with clonal B-cells; Increase of ≥ 25% bone marrow involvement; ≥ 25% increase in blood involvement with clonal B-cells.
AML/ALL: Any incidence of relapse (>5% blasts) by evaluation of the bone marrow aspirate.
CML: Inability to control platelet or granulocyte counts; Increase in baseline number of metaphases demonstrating the Ph+ chromosome by >25%; Any other new cytogenetic abnormality; Transformation to accelerated phase or blast crisis.
MDS/MPD: Any evidence by morphologic or flow cytometric evaluation of the bone marrow aspirate of new blasts (>5%) or worsening cytopenia or cytogenetic evidence of recurrence.
Measured: Years 1, 2, 3, and 5
Relapse Mortality
The percentage of patients (out of 147 participants) who relapsed at Years 1 and 2. Relapse is defined as the presence of >5% blasts by morphology on a post-transplant bone marrow aspirate.
Measured: Years 1 and 2
Acute Graft-Versus-Host Disease (aGVHD) Outcome
Grading of Acute GVHD:
Severity of Individual Organ Involvement:
Skin
- 1 a maculopapular eruption involving less than 25% of the body surface
- 2 a maculopapular eruption involving 25-50% of the body surface
- 3 generalized erythroderma
- 4 generalized erythroderma with bullous formation and/or with desquamation Liver
- 1 bilirubin 2.0-3.0mg/100mL
- 2 bilirubin 3-5.9mg/100mL
- 3 bilirubin 6-14.9mg/100mL
- 4 bilirubin >15mg/100mL Gut Diarrhea is graded +1 to +4 in severity. Nausea/vomiting and/or anorexia caused by GVHD is assigned as +1 in severity Diarrhea
- 1 <1000mL of liquid stool/day
- 2 >1,000mL of stool/day
- 3 >1,500mL of stool/day
- 4 2,000mL of stool/day, severe abdominal pain, with or without ileus
Severity of GVHD:
Grade 1 +1 to +2 skin rash; No gut or liver involvement Grade 2 +1 to +3 skin rash;+1 GI involvement and/or +1 liver
Measured: Day 100, Month 6
Chronic Graft-Versus-Host Disease (cGVHD) Outcome
Grading of Chronic GVHD:
Limited: Localized skin involvement and/or hepatic dysfunction due to chronic GVHD
Extensive:
One or more of the following:
Generalized skin involvement Liver histology showing chronic aggressive hepatitis, bridging necrosis or cirrhosis Involvement of the eye: Schirmer's test with <5 mm wetting Involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy Involvement of any other target organ
Chronic GVHD Severity:
Mild: Signs and symptoms of cGVHD do not interfere substantially with function and do not progress once appropriately treated with local therapy or standard systemic therapy.
Moderate: Signs and symptoms of cGVHD interfere somewhat with function despite appropriate therapy or are progressive through first line systemic therapy.
Severe: Signs and symptoms of cGVHD limit function substantially despite appropriate therapy or are progressive through second line systemic therapy
Measured: Years 1, 2 and 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2005 (estimated)
- Study startJun 2005
- Primary completionAug 2015
- Study completionAug 2015
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 OHSU Knight Cancer InstituteThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Richard Maziarz, OHSU Knight Cancer Institute
- Investigators
- Richard Maziarz, MD, Study chair, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00245037
- Sponsor's protocol ID
- IRB00000210
- Other IDs
- P30CA016058, OHSU-HEM-05011-L, OHSU-210
- Acronym
- Bu Flu TBI
- Status last verified
- Sep 2017
- First submitted
- 25 Oct 2005
- Last updated
- 27 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of Patients With Hematologic Malignancies Using Busulfan, Fludarabine and Total Body Irradiation
- ClinicalTrials.gov ID
- NCT00245037
- Acronym / sponsor ID
- Bu Flu TBI / IRB00000210
- Conditions
- Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Keywords
- recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, breakpoint cluster region-Abelson (BCR-ABL) negative, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jun 2005
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 27 Oct 2005 (estimated)
- Results
- Posted 2 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood 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 may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving busulfan and fludarabine together with total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell transplant for hematologic cancer.
Detailed description
OBJECTIVES:
Primary
- To assess safety and toxicity of the addition of busulfan added to an established fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for non-myeloablative allogeneic transplantation in patients with hematologic malignancies. (Phase I)
- To assess the non-relapse mortality 1-year after conditioning with busulfan and fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease. (Phase II)
Secondary
- To assess overall survival 1-year survival. (Phase II)
- To assess the incidence of graft rejection. (Phase II)
- To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic extensive GVHD. (Phase II)
- To assess rates of disease progression and/or relapse-related mortality. (Phase II)
- To determine non-hematologic grade III-IV organ specific toxicity. (Phase II)
OUTLINE:
- Nonmyeloablative-conditioning regimen: Patients receive busulfan IV on day -5 and fludarabine IV over 30 minutes on days -4 to -2. Patients undergo total body irradiation on day 0.
- Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo donor PBSC infusion on day 0.
- Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180. Patients with a related stem cell donor receive oral mycophenolate mofetil twice daily on days 0-28. Patients with an unrelated stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed by a taper twice daily to day 56. Patients with evidence of relapse or persistent disease may also receive up to 3 donor lymphocyte infusions.
PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study; 25 patients accrued into the Phase I and 200 patients into Phase II.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) | Experimental | Biological: therapeutic allogeneic lymphocytes, Drug: busulfan, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: mycophenolate mofetil, Procedure: peripheral blood stem cell transplantation, Radiation: Total Body Irradiation (TBI), Drug: Granulocyte colony-stimulating factor (G-CSF), Drug: Phenytoin, Drug: MethotrexateBusulfan 3.2 mg/kg IV on day -5 Fludarabine 30 mg/m2/day x 3 (total dose 90 mg/m2, day -4 to day -2 TBI 200 centigray (cGy) x 1, day 0 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| therapeutic allogeneic lymphocytesA population of lymphocytes therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species. | Biological | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| busulfanBusulfan is an alkylating chemotherapeutic agent which has been used in many high dose and reduced intensity regimens prior to allogeneic or autologous hematopoietic stem cell transplants. It is active in a wide variety of malignancies and in high-doses it is myeloablative. IV busulfan is available and diluted and administered per package insert guidelines. | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| cyclosporineCyclosporine is a cyclic polypeptide immunosuppressive agent. It blocks the calcium-dependent calcineurin-mediated nuclear localization of nuclear factor of activated T cells (NFAT) following T-cell activation, thereby inhibiting transactivation of key T-cell response genes including Interleukin 2 (IL-2) and Interleukin 4 (IL-4). - Starting on day -3, Cyclosporine (CSP) is given at a dose of 4.0 mg/kg p.o. b.i.d. | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| fludarabine phosphateFludarabine's active metabolite 2-fluoro-ara-A is an antimetabolite that inhibits DNA primase, DNA polymerase alpha and ribonucleotide nuclease. * Dosing: Days -4, -3 and -2: Fludarabine 30 mg/m2/day IV. Total dose equals 90 mg/m2. * Monitoring: Fludarabine level is not monitored. * Dose Adjustments: There are no provisions for fludarabine dose adjustments. | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| mycophenolate mofetilMycophenolate mofetil (MMF) is the morpholinyl ethyl ester of mycophenolic acid (MPA) and reversibly inhibits inosine monophosphate dehydrogenase, particularly the type II isoform that is more prominent in activated lymphocytes. As a result of the inhibition of de novo purine synthesis, proliferation of B- and T-lymphocytes is blocked and antibody production is inhibited. * Related Donors: MMF will be given daily at 15mg/kg q 12 hrs until day +28, then stop without tapering. Doses will be rounded to the nearest 250 mg (capsules are 250 mg). * Unrelated Donors: MMF will be given daily at 15mg/kg q 8 hrs until day +28, then given daily at 15mg/kg q 12 hours until day +56, then stop without tapering. Doses will be rounded to the nearest 250 mg (capsules are 250 mg). | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| peripheral blood stem cell transplantationBone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures that restore stem cells that have been destroyed by high doses of chemotherapy and/or radiation therapy. There are three types of transplants: * In autologous transplants, patients receive their own stem cells. * In syngeneic transplants, patients receive stem cells from their identical twin. * In allogeneic transplants, patients receive stem cells from their brother, sister, or parent. A person who is not related to the patient (an unrelated donor) also may be used. | Procedure or surgery | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| Total Body Irradiation (TBI)TBI is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell (or bone marrow) transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lungs are often partially shielded to lower the risk of radiation-induced lung injury. * Toxicities: At the dosage used, side effects are not expected. Nevertheless, there may be fever, alopecia, parotitis, diarrhea, reversible skin pigmentation, mucositis and late effects including cataract formation, pulmonary damage, carcinogenesis, and sterilization. * Dosing: TBI will be given in one 200 cGy fraction from linear accelerator at a rate of 15-19 cGy/min. | Radiation | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| Granulocyte colony-stimulating factor (G-CSF)Granulocyte colony-stimulating factor (G-CSF or GCSF) is a colony-stimulating factor hormone. G-CSF is also known as colony-stimulating factor 3 (CSF 3). It is a glycoprotein, growth factor and cytokine produced by a number of different tissues to stimulate the bone marrow to produce granulocytes and stem cells. G-CSF then stimulates the bone marrow to release them into the blood. * Toxicities: At the dosage used, the most common side effect will be medullary bone pain. * Dosing: 5 mcg/kg/day given per institutional standards (on approximately days 10-15 or not at all). | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| PhenytoinThis drug is used to prevent seizures while on chemotherapy. | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
| MethotrexateMethotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body) that cannot be controlled by other treatments. | Drug | Busulfan (Bu), Fludarabine (Flu), Total Body Iradiation (TBI) |
Primary outcome
Regimen-Related Toxicities
Time frame: 5 years post-transplant
Non-hematologic toxicities and adverse experiences ≥ Grade 3 occurrences measured up to day +100 using the NCI Common Toxicity Criteria for Adverse Events v3.0 (CTCAE). Infections and GVHD will be assessed up to 5 years post transplant. The following data represents the number of regimen-related, grade 3 and 4 toxicities that occurred in each category.
Non-relapse Mortality
Time frame: Two years post-transplant
Percent of subjects with non-relapse mortality two years after conditioning with busulfan with fludarabine/200 cGy TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease.
5 secondary outcomes
Overall Survival
Time frame: Years 1, 2, 3 and 5
Progression-Free Survival
Time frame: Years 1, 2, 3, and 5
Relapse Mortality
Time frame: Years 1 and 2
Acute Graft-Versus-Host Disease (aGVHD) Outcome
Time frame: Day 100, Month 6
Chronic Graft-Versus-Host Disease (cGVHD) Outcome
Time frame: Years 1, 2 and 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
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.
Richard Maziarz, MD study chair
OHSU Knight Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing therapeutic allogeneic lymphocytes, busulfan and cyclosporine in people with Chronic Myeloproliferative Disorders and Leukemia, run by OHSU Knight Cancer Institute 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?
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 27 Sep 2017. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 2 Jul 2017). 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?
Regimen-Related Toxicities (time frame: 5 years post-transplant). The study lists 2 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 27 Sep 2017.