LeukemiaPhase 2NCT00054327
Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
A Phase 2 study testing busulfan, cyclophosphamide and cytarabine in people with Leukemia and Lymphoma, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer and abnormal cells and 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 55 years
- Conditions the study is for
- Leukemia, Lymphoma, Myelodysplastic Syndromes
- What is being tested?
- busulfan, cyclophosphamide and cytarabine
- 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
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2000to Sep 2011
- 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
Eligibility Criteria:
- Patients with histologic confirmation of the following diseases are eligible:
- AML in first, second or greater remission
- AML in early relapse, defined at <30% marrow blasts
- ALL in second or greater complete remission
- High risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22), or t(8;14) translocation, or patients presenting with extreme hyperleukocytosis (initial WBC >500 K/ml) or failure to achieve a complete remission after standard induction therapy.
- CML
- Myelodysplastic syndromes (including evolution to AML, e.g., Refractory Anemia with Excess Blasts (RAEB), or Refractory Anemia with Excess Blasts in transformation (RAEB-t).
- Lymphoma (intermediate and high grade) chemosensitive (CR or PR) after first or greater relapse or chemosensitive to first line therapy but only achieving PR.
- Hematologic Disease and Inherited Immunodeficiencies
- Hodgkin's disease, relapsed or refractory to standard treatments.
- Patients must be less than or equal to 55 years of age.
- Patients (or guardians if minor) must be able to give informed consent. Children older than 11 years of age must assent to the process.
- Patients or their guardians must demonstrate proof-of-payment.
- Patients must have an ECOG Performance Status of 2 or less. (See Appendix I)
- Patients must have no evidence of active infection at the time of transplantation.
- Patients must be HIV nonreactive.
- Patients must have a pre-transplant, multi-organ assessment prior to transplantation with the following outcome:
- resting ejection fraction of 50% or greater (or shortening fraction greater than 28% for small children).
- Diffusion capacity of 50% or greater of predicted, a FEV1 of 50% or greater, and a P2O of 80 mm Hg as demonstrated on pulmonary function testing.
- serum creatinine of less than or equal to 2.0 mg/dL and/or a corrected creatinine clearance of 50 ml/min or greater on 24 hr urine.
- A total bilirubin of less than 2.5 mg/dL and an AST less than 4 times the upper limits of normal.
- Females who are childbearing age may not be pregnant or lactating and must have a current negative pregnancy test
Ineligibility Criteria:
- Patients who have a life expectancy of less than three months with therapy.
- Patients who have an ECOG performance status greater than 2, (See Appendix I) or Lansky Scale < 70%.
- Patients who have angina and/or congestive heart failure requiring treatment, or who have had a myocardial infarction within the past year.
- Patients who have a resting ejection of less than 50% (or shortening fraction less than 28%) and who have not been cleared for transplant by cardiology
- Patients who have severe renal disease as demonstrated by a serum creatinine greater than 2.0 mg/dL and/or a corrected creatinine clearance less than 50 ml/min. (corrected for BSA of 1.73 m¬2)
- Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse.
- Patients who have any active infection such as a soft tissue infection, sinus infection, dental infection, fungal infection or hepatitis including chronic active hepatitis; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date.
- Patients who have decreased pulmonary function due to any disorder as demonstrated by a diffusion capacity of less than 50% of predicted, a FEV1 of less than 50% of predicted or a PO2 of less than 80 mm Hg pulmonary function testing.
- Patients who have decreased liver function as demonstrated by a total bilirubin of greater than 2.5 mg/dL and/or an AST greater than 4 times the upper limits of normal.
- Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.
-Patients who have a significant psychiatric illness will be considered on a case- by-case basis. With the patient's consent, their Mental Health Care worker will assist the managing transplant physicians in determining if the patient can safely undergo transplantation and comply with followup recommendations.
- Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated. This decision will be based upon estimated adequacy of patient support systems and prediction of patient's compliance with medications, required diagnostic procedures and/or follow-up care.
- Females who are childbearing age may not be pregnant or lactating and must have a current negative pregnancy test
- Patients who had a stem cell transplant less than one year earlier
Trial locations and contacts
1 site in 1 country.
United States1 site
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
About this study
Official title: Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PURPOSE: This phase II trial is studying how well giving chemotherapy with or without radiation therapy followed by donor stem cell transplant works in treating patients with hematologic cancer.
Read the detailed description
OBJECTIVES:
- Determine a standard approach to hematopoietic stem cell transplantation with matched unrelated donors in patients with hematologic malignancies.
- Determine the toxicity of this regimen in these patients.
- Determine the relapse rate and survival rate in patients treated with this regimen.
- Correlate incidence and severity of graft-versus-host disease with relapse and survival in patients treated with this regimen.
OUTLINE: Patients receive 1 of the following preparative regimens:
- Regimen A: Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.
- Regimen B-1: Patients receive cyclophosphamide IV and TBI as in regimen A.
- Regimen B-2: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.
- Regimen B-3: Patients receive TBI on days -7 to -5. Patients receive cyclophosphamide IV over on days -4 to -3.
- Regimen C: Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.
- Regimen D: Patients receive TBI on days -6 to -4. Patients receive etoposide infusion on day -3.
All patients undergo stem cell transplantation from a matched, unrelated donor on day 0.
Patients are followed weekly for 100 days, at 6 months, and then every 6 months for 2.5 years.
PROJECTED ACCRUAL: 50
- Conditions
- Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Being tested
- busulfan, cyclophosphamide, cytarabine, radiation therapy, Etoposide
- Keywords
- adult acute myeloid leukemia in remission, childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 3 follicular lymphoma, secondary acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, recurrent childhood large cell lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
busulfanDrug
Also called Myleran
Given orally 1mg/kg/dose (or 40mg/m2/dose for young children)
cyclophosphamideDrug
Also called cytoxan, CTX, CPM
Given IV
cytarabineDrug
Also called Cytosine Arabinoside, Cytosar-U, Ara-C, Arabinosyl
Given IV
radiation therapyRadiation
Also called Total body irradiation
Patients undergo total body irradiation
EtoposideDrug
Also called VP-16, VePesid®, VP-16-213, EPEG
infusion
Stem Cell TransfusionProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Regimen A | Experimental | Patients receive cytarabine 3.0gm/M² IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide 45mg/kg IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI), 165 cGY, twice daily on days -4 to -1 for a total of 1320 cGY. Receives: Drug: cyclophosphamide; Drug: cytarabine; Radiation: radiation therapy; Procedure: Stem Cell Transfusion |
| Regimen B-1 | Experimental | Patients receive cyclophosphamide 60 mg/kg IV on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1 for a total of 1320 cGY.. Receives: Drug: cyclophosphamide; Radiation: radiation therapy; Procedure: Stem Cell Transfusion |
| Regimen B-2 | Experimental | Patients receive cyclophosphamide 60 mg/kg IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1 for a total of 1200 cGY. Receives: Drug: cyclophosphamide; Radiation: radiation therapy; Procedure: Stem Cell Transfusion |
| Regimen C | Experimental | Patients receive oral busulfan 1mg/kg/dose (or 40mg/m2/dose for young children)4 times daily on days -8 to -5 and cyclophosphamide 60 mg/kg IV over 2 hours on days -4 to -2. Receives: Drug: busulfan; Drug: cyclophosphamide; Procedure: Stem Cell Transfusion |
| Regimen B-3 | Experimental | Patients undergo total body irradiation (TBI) twice daily on days -7 to -5 for a total of 1200 cGY. Patients then receive cyclophosphamide 60 mg/kg IV on days -4 and -3. Receives: Drug: cyclophosphamide; Radiation: radiation therapy; Procedure: Stem Cell Transfusion |
| Regimen D | Experimental | Patients receive total body irradiation (TBI) on days T -6, -5 and -4 for a total of 1320 cGy , then etoposide (60mg/kg/dose) on day -3. Receives: Radiation: radiation therapy; Drug: Etoposide; Procedure: Stem Cell Transfusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of Durable Engraftment
Number of days that patients take to reach engraftment defined as time to hematologic engraftment will be defined as ANC >500/µl and platelets >20K/µl without transfusion support.
Measured: at day 42
Secondary outcomes (3)
Graft-versus-host Disease (GVHD)
Number of patients that develop acute graft-versus-host disease by grades 0-4. Grade O is no development of GVHD. Grade 1-4 is increase severity of skin, liver and gut involvement with 1 being least severe and 4 being most severe.
Measured: at 100 days post transplant
Incidence of Recurrent Disease
Number of patients that have disease recurrence.
Measured: at day 100 post transplant
Toxicity as Measured by CTC v2.0
Number of patients that experience grade 3 or above toxicity. See serious adverse event list for toxicities.
Measured: at 100 days post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2003 (estimated)
- Study startNov 2000
- Primary completionSep 2011
- Study completionSep 2011
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 Case Comprehensive Cancer CenterThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kenneth Cooke, MD, Principal investigator, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00054327
- Sponsor's protocol ID
- CWRU1Y00
- Other IDs
- P30CA043703, CASE-CWRU-1Y00
- Status last verified
- Jun 2013
- First submitted
- 5 Feb 2003
- Last updated
- 24 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors
- ClinicalTrials.gov ID
- NCT00054327
- Acronym / sponsor ID
- CWRU1Y00
- Conditions
- Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
- Keywords
- adult acute myeloid leukemia in remission, childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2000
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 6 Feb 2003 (estimated)
- Results
- Posted 24 Jul 2013
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 and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PURPOSE: This phase II trial is studying how well giving chemotherapy with or without radiation therapy followed by donor stem cell transplant works in treating patients with hematologic cancer.
Detailed description
OBJECTIVES:
- Determine a standard approach to hematopoietic stem cell transplantation with matched unrelated donors in patients with hematologic malignancies.
- Determine the toxicity of this regimen in these patients.
- Determine the relapse rate and survival rate in patients treated with this regimen.
- Correlate incidence and severity of graft-versus-host disease with relapse and survival in patients treated with this regimen.
OUTLINE: Patients receive 1 of the following preparative regimens:
- Regimen A: Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.
- Regimen B-1: Patients receive cyclophosphamide IV and TBI as in regimen A.
- Regimen B-2: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.
- Regimen B-3: Patients receive TBI on days -7 to -5. Patients receive cyclophosphamide IV over on days -4 to -3.
- Regimen C: Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.
- Regimen D: Patients receive TBI on days -6 to -4. Patients receive etoposide infusion on day -3.
All patients undergo stem cell transplantation from a matched, unrelated donor on day 0.
Patients are followed weekly for 100 days, at 6 months, and then every 6 months for 2.5 years.
PROJECTED ACCRUAL: 50
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Regimen A | Experimental | Drug: cyclophosphamide, Drug: cytarabine, Radiation: radiation therapy, Procedure: Stem Cell TransfusionPatients receive cytarabine 3.0gm/M² IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide 45mg/kg IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI), 165 cGY, twice daily on days -4 to -1 for a total of 1320 cGY. |
| Regimen B-1 | Experimental | Drug: cyclophosphamide, Radiation: radiation therapy, Procedure: Stem Cell TransfusionPatients receive cyclophosphamide 60 mg/kg IV on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1 for a total of 1320 cGY.. |
| Regimen B-2 | Experimental | Drug: cyclophosphamide, Radiation: radiation therapy, Procedure: Stem Cell TransfusionPatients receive cyclophosphamide 60 mg/kg IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1 for a total of 1200 cGY. |
| Regimen C | Experimental | Drug: busulfan, Drug: cyclophosphamide, Procedure: Stem Cell TransfusionPatients receive oral busulfan 1mg/kg/dose (or 40mg/m2/dose for young children)4 times daily on days -8 to -5 and cyclophosphamide 60 mg/kg IV over 2 hours on days -4 to -2. |
| Regimen B-3 | Experimental | Drug: cyclophosphamide, Radiation: radiation therapy, Procedure: Stem Cell TransfusionPatients undergo total body irradiation (TBI) twice daily on days -7 to -5 for a total of 1200 cGY. Patients then receive cyclophosphamide 60 mg/kg IV on days -4 and -3. |
| Regimen D | Experimental | Radiation: radiation therapy, Drug: Etoposide, Procedure: Stem Cell TransfusionPatients receive total body irradiation (TBI) on days T -6, -5 and -4 for a total of 1320 cGy , then etoposide (60mg/kg/dose) on day -3. |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| busulfanAlso: MyleranGiven orally 1mg/kg/dose (or 40mg/m2/dose for young children) | Drug | Regimen C |
| cyclophosphamideAlso: cytoxan, CTX, CPMGiven IV | Drug | Regimen A, Regimen B-1, Regimen B-2, Regimen B-3, Regimen C |
| cytarabineAlso: Cytosine Arabinoside, Cytosar-U, Ara-C, ArabinosylGiven IV | Drug | Regimen A |
| radiation therapyAlso: Total body irradiationPatients undergo total body irradiation | Radiation | Regimen A, Regimen B-1, Regimen B-2, Regimen B-3, Regimen D |
| EtoposideAlso: VP-16, VePesid®, VP-16-213, EPEGinfusion | Drug | Regimen D |
| Stem Cell Transfusion | Procedure or surgery | Regimen A, Regimen B-1, Regimen B-2, Regimen B-3, Regimen C, Regimen D |
Primary outcome
Rates of Durable Engraftment
Time frame: at day 42
Number of days that patients take to reach engraftment defined as time to hematologic engraftment will be defined as ANC >500/µl and platelets >20K/µl without transfusion support.
3 secondary outcomes
Graft-versus-host Disease (GVHD)
Time frame: at 100 days post transplant
Incidence of Recurrent Disease
Time frame: at day 100 post transplant
Toxicity as Measured by CTC v2.0
Time frame: at 100 days post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2013.
- 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.
Kenneth Cooke, MD principal investigator
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
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 cytarabine in people with Leukemia and Lymphoma, run by Case Comprehensive Cancer Center 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 24 Jul 2013. 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 24 Jul 2013). 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?
Rates of Durable Engraftment (time frame: at day 42). 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 24 Jul 2013.