LeukemiaPhase 2NCT00028730
Total-Body Irradiation and Chemotherapy Followed By Donor Bone Marrow Transplant in Treating Young Patients With Hematologic Cancer
A Phase 2 study testing anti-thymocyte globulin, filgrastim and cyclophosphamide in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow 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 18 years
- Conditions the study is for
- Leukemia, Lymphoma, Myelodysplastic Syndromes
- What is being tested?
- anti-thymocyte globulin, filgrastim and cyclophosphamide
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2001to Jun 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- One of the following diagnoses:
- Histologically confirmed good-risk acute myeloid leukemia (AML) in first remission with an HLA-compatible related donor
- Ineligible for unrelated bone marrow transplantation unless failed first-line induction chemotherapy or have molecular evidence of disease at time of transplantation
- Histologically confirmed high-risk AML in first remission
- High risk defined by cytogenetics, biphenotypic and undifferentiated leukemia phenotype, secondary AML, or AML after myelodysplastic syndromes (MDS)
- Eligible for related or unrelated donor transplantation
- Histologically confirmed acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) in first remission with high risk for relapse or in second or third remission
- High risk for relapse defined by hypodiploidy, pseudodiploidy with translocations t(9;22) or infant t(4;11), or failure to achieve remission after four weeks of induction therapy
- Eligible for related or unrelated donor transplantation
- Histologically confirmed chronic myelogenous leukemia (CML) in at least first chronic phase or acceleration with an HLA-compatible related donor
- Histologically confirmed CML in first chronic phase if failed conventional therapy or in at least second chronic phase or acceleration with an HLA-compatible unrelated donor
- Histologically confirmed non-Hodgkin's lymphoma beyond first complete remission or primary induction failure and tumors that are chemosensitive defined as at least 50% reduction in mass size
- Eligible for related or unrelated donor transplantation
- Histologically confirmed MDS with intermediate or high-risk disease defined by International Prognostic Scoring System and paroxysmal nocturnal hematuria
- Eligible for related or unrelated donor transplantation
- Treatment-related MDS or leukemia allowed if primary malignancy (e.g., neuroblastoma or Ewing's sarcoma) at low risk of recurrence
- No AML, ALL, or LL in relapse or greater than third remission
- No CML in blast crisis defined as more than 30% blasts plus promyelocytes
- No active CNS involvement
- History of leukemia cutis allowed
- HLA compatible donor available
- 5/6 or 6/6 HLA antigen matched related or unrelated
PATIENT CHARACTERISTICS:
Age:
- 18 and under
Performance status:
- Karnofsky 70-100% OR
- Lansky 50-100%
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- Bilirubin no greater than 2.5 times upper limit of normal (ULN)
- AST no greater than 3 times ULN (unless liver involvement is present)
Renal:
- Creatinine normal OR
- Creatinine clearance greater than 60 mL/min
Cardiovascular:
- LVEF at least 50% at rest (if less than 50% at rest, must increase with exercise)
Pulmonary:
- Asymptomatic with no prior risk features OR
- DLCO greater than 40% predicted (corrected for hemoglobin) if symptomatic
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV I/II negative
- No uncontrolled viral, bacterial, or fungal infection
- No known hypersensitivity to bovine proteins
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characterisitics
Chemotherapy:
- See Disease Characteristics
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior radiotherapy that would preclude total body irradiation dose
Surgery:
- Not specified
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
Official title: Phase II Trial of T-Cell Depleted Hematopoietic Stem Cell Transplants (SBA-E-BM) From HLA Compatible Related or Unrelated Donors After a Myeloablative Preparative Regimen of Hyperfractionated TBI, Thiotepa and Cyclophosphamide (TBI/Thio/cy) for Treatment of Patients Less Than or Equal to 18 Years With Lymphohematopoietic Disorders
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow 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 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 antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well total-body irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplant works in treating young patients with hematologic cancer.
Read the detailed description
OBJECTIVES:
- Determine the efficacy of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide followed by T-cell-depleted allogeneic bone marrow transplantation in children with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, or myelodysplastic syndromes.
- Correlate the progenitor cell dose and dose of clonable T cells with the incidence and quality of engraftment, extent of chimerism, incidence and severity of acute and chronic graft-versus-host disease, characteristics of hematopoietic and immunologic reconstitution, and overall and disease-free survival at 2 years in patients treated with this regimen.
OUTLINE: Patients undergo total body irradiation three times daily on days -9 to -7 and twice on day -6. Patients receive thiotepa IV over 4 hours on days -5 and -4 and cyclophosphamide IV over 30 minutes on days -3 and -2. Patients who cannot receive cyclophosphamide, due to prior hemorrhagic cystitis or exposure to high-dose cyclophosphamide or ifosfamide, receive fludarabine IV over 30 minutes on days -5 to -1. Patients planning to receive family member HLA-mismatched or unrelated bone marrow transplantation receive horse anti-thymocyte globulin IV once daily on days -5 and -4. Patients undergo allogeneic T-cell-depleted bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) IV every 12 hours beginning on day 7 and continuing until blood counts recover.
Patients are followed every 2-4 weeks for the first 100 days post-transplantation, every 6 weeks for 6 months, every 3 months for 1 year, and then every 3-6 months until 2 years post-transplantation.
PROJECTED ACCRUAL: A total of 50 patients (25 with HLA 6/6 antigen-matched related donors and 25 with HLA 5/6 antigen-matched related donors or HLA 5/6 or 6/6 antigen-matched unrelated donors) will be accrued for this study within 3 years.
- Conditions
- Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Being tested
- anti-thymocyte globulin, filgrastim, cyclophosphamide, fludarabine phosphate, thiotepa
- Keywords
- recurrent childhood lymphoblastic lymphoma, chronic phase chronic myelogenous leukemia, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, myelodysplastic/myeloproliferative neoplasm, unclassifiable
- Medical subject headings
- Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Leukemia, Myeloid, Chronic-Phase, Burkitt Lymphoma, Dendritic Cell Sarcoma, Interdigitating, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
filgrastimBiological
cyclophosphamideDrug
thiotepaDrug
allogeneic bone marrow transplantationProcedure or surgery
radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Pts < than or = 18 years with lymphohematopoietic disorders | Experimental | This is a phase II, single-center study to evaluate a cytoreductive regimen of hyperfractionated TBI, thiotepa and cyclophosphamide (HFTBI/thio/cy) followed by infusions of SBA-E- T-cell depleted marrow in pediatric leukemia recipients of either HLA-identical or HLA-1Ag non-identical related or unrelated donors. Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: thiotepa; Procedure: allogeneic bone marrow transplantation; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal transplantation related mortality
Measured: 2 years
High disease-free survival at 2 years
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startAug 2001
- Primary completionJul 2006
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Nancy A. Kernan, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00028730
- Sponsor's protocol ID
- 01-105
- Other IDs
- P30CA008748, P01CA033049, P01CA023766, MSKCC-01105, NCI-H01-0083
- Status last verified
- Dec 2015
- First submitted
- 4 Jan 2002
- Last updated
- 22 Dec 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of T-Cell Depleted Hematopoietic Stem Cell Transplants (SBA-E-BM) From HLA Compatible Related or Unrelated Donors After a Myeloablative Preparative Regimen of Hyperfractionated TBI, Thiotepa and Cyclophosphamide (TBI/Thio/cy) for Treatment of Patients Less Than or Equal to 18 Years With Lymphohematopoietic Disorders
- ClinicalTrials.gov ID
- NCT00028730
- Acronym / sponsor ID
- 01-105
- Conditions
- Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
- Keywords
- recurrent childhood lymphoblastic lymphoma, chronic phase chronic myelogenous leukemia, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Aug 2001
- Primary completion
- Jul 2006 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
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 bone marrow 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 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 antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well total-body irradiation and chemotherapy followed by T-cell depleted donor bone marrow transplant works in treating young patients with hematologic cancer.
Detailed description
OBJECTIVES:
- Determine the efficacy of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide followed by T-cell-depleted allogeneic bone marrow transplantation in children with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, or myelodysplastic syndromes.
- Correlate the progenitor cell dose and dose of clonable T cells with the incidence and quality of engraftment, extent of chimerism, incidence and severity of acute and chronic graft-versus-host disease, characteristics of hematopoietic and immunologic reconstitution, and overall and disease-free survival at 2 years in patients treated with this regimen.
OUTLINE: Patients undergo total body irradiation three times daily on days -9 to -7 and twice on day -6. Patients receive thiotepa IV over 4 hours on days -5 and -4 and cyclophosphamide IV over 30 minutes on days -3 and -2. Patients who cannot receive cyclophosphamide, due to prior hemorrhagic cystitis or exposure to high-dose cyclophosphamide or ifosfamide, receive fludarabine IV over 30 minutes on days -5 to -1. Patients planning to receive family member HLA-mismatched or unrelated bone marrow transplantation receive horse anti-thymocyte globulin IV once daily on days -5 and -4. Patients undergo allogeneic T-cell-depleted bone marrow transplantation on day 0. Patients receive filgrastim (G-CSF) IV every 12 hours beginning on day 7 and continuing until blood counts recover.
Patients are followed every 2-4 weeks for the first 100 days post-transplantation, every 6 weeks for 6 months, every 3 months for 1 year, and then every 3-6 months until 2 years post-transplantation.
PROJECTED ACCRUAL: A total of 50 patients (25 with HLA 6/6 antigen-matched related donors and 25 with HLA 5/6 antigen-matched related donors or HLA 5/6 or 6/6 antigen-matched unrelated donors) will be accrued for this study within 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pts < than or = 18 years with lymphohematopoietic disorders | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: cyclophosphamide, Drug: fludarabine phosphate, Drug: thiotepa, Procedure: allogeneic bone marrow transplantation, Radiation: radiation therapyThis is a phase II, single-center study to evaluate a cytoreductive regimen of hyperfractionated TBI, thiotepa and cyclophosphamide (HFTBI/thio/cy) followed by infusions of SBA-E- T-cell depleted marrow in pediatric leukemia recipients of either HLA-identical or HLA-1Ag non-identical related or unrelated donors. |
Who may qualify
- Ages
- Up to 18 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 |
|---|---|---|
| anti-thymocyte globulin | Biological | Pts < than or = 18 years with lymphohematopoietic disorders |
| filgrastim | Biological | Pts < than or = 18 years with lymphohematopoietic disorders |
| cyclophosphamide | Drug | Pts < than or = 18 years with lymphohematopoietic disorders |
| fludarabine phosphate | Drug | Pts < than or = 18 years with lymphohematopoietic disorders |
| thiotepa | Drug | Pts < than or = 18 years with lymphohematopoietic disorders |
| allogeneic bone marrow transplantation | Procedure or surgery | Pts < than or = 18 years with lymphohematopoietic disorders |
| radiation therapy | Radiation | Pts < than or = 18 years with lymphohematopoietic disorders |
Primary outcome
Minimal transplantation related mortality
Time frame: 2 years
High disease-free survival at 2 years
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2015.
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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.
Nancy A. Kernan, MD study chair
Memorial Sloan Kettering 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 anti-thymocyte globulin, filgrastim and cyclophosphamide in people with Leukemia and Lymphoma, run by Memorial Sloan Kettering 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 22 Dec 2015. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Minimal transplantation related mortality (time frame: 2 years). 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 22 Dec 2015.