LeukemiaPhase 2NCT00739141
Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.
A Phase 2 study testing fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft in people with Leukemia and Myelodysplastic Syndrome, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The traditional way of doing a donor transplant is to give high doses of chemotherapy and radiation before giving the stem cells. However, high doses of chemotherapy and radiation can have serious side-effects. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndrome, Non-Hodgkins Lymphoma
- What is being tested?
- fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2008to 15 Oct 2021
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy or azacitidine or decitabine or tyrosine kinase inhibitor.
- Patients aged 18-70 years at initial referral with no available and suitably matched related or unrelated donor.
- Acute myelogenous leukemia (AML):
- Complete first remission (CR1) at high risk for relapse such as:
- Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder;
- Therapy related AML;
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- White cell count at presentation > 100,000;
- Presence of extramedullary leukemia at diagnosis;
- Any unfavorable sub type by FAB or WHO classification;
- High-risk cytogenetics (eg those associated with MDS, abnormalities of 5, 7, 8, Philadelphia chromosome, complex karyotype)or high risk molecular abnormalities;
- Requirement for 2 or more inductions to achieve CR1.
- Any patient with newly diagnosed AML with intermediate risk cytogenetics.
- Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician.
- Complete second remission (CR2).
- Other acute leukemias that are ambiguous lineage or of other types eg blastic plasmacytoid dendritic cell neoplasm in CR1 or CR2
- Acute lymphoblastic leukemia (ALL):
- lymphoblastic leukemia (ALL):
- Complete first remission (CR1) at high risk for relapse such as:
- White cell count at presentation > 30,000 for B-cell lineage and >100,000 for Tcell lineage;
- Presence of a high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23)or other high-risk molecular abnormality;
- Failure to achieve complete remission after four weeks of induction therapy;
- Any patient with newly diagnosed ALL > or = to 50 years-old;
- Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.
- Complete second remission (CR2).
- Myelodysplastic Syndrome (MDS):
- Intermediate-1 International Prognostic Scoring System (IPSS) score with poor risk cytogenetics as defined by IPSS.
- Intermediate- 2 or High International Prognostic Scoring System (IPSS) score.
- MDS/ myeloproliferative disorder overlap syndromes.
- Any score with life threatening cytopenia(s), including red cell or platelet transfusion dependence.
- Receipt of at least one cycle of cytotoxic chemotherapy, azacitidine or decitabine.
- MDS patients must have < or = to 5% bone marrow myeloblasts and ANC > or = to 0.2 (growth factor supported if necessary) at transplant work-up.
- Myeloproliferative Disorder (MPD)
- Life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence
- Patients with aplasia
- Patients with excess blasts less than or equal to 10% blasts in the bone marrow at work-up.
- Chronic myelogenous leukemia (CML) patients who have failed or are intolerant of tyrosine kinase inhibitors or patients with other myeloproliferative diseases who are high risk and the intent of therapy is cure.
- Any Non-Hodgkins lymphoma (including chronic lymphocytic leukemia)or Hodgkin's lymphoma at high-risk of relapse
- Eligible patients with DLC NHL will:
- have relapsed disease following initial therapy but failed to mobilize or had bone marrow involvement and therefore are not suitable for an autologous transplant OR
- have failed an autologous transplant and be in CR after salvage chemotherapy.
- Eligible patients with transformed indolent NHL/CLL will:
- have CR/PR of the large cell component of their disease after either salvage chemotherapy or an autologous transplant.
- Eligible patients with mantle cell NHL will:
- be high-risk as such as p53 positivity and be in 1st CR/PR after initial therapy OR have relapsed disease following initial therapy and be in 2nd or 3rd CR/PR after salvage chemotherapy.
- Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) or CLL will have 2nd or subsequent progression (pre-allograft cytoreduction necessary but CR/PR not required).
- Eligible patients with HL will be without progression of disease (POD) after salvage chemotherapy.
- Timing of UCBT:
- Admission for UCBT must be within an acceptable time period after the pre-allograft chemotherapy.
- Organ Function and Performance Status Criteria:
- Karnofsky score > or = to 70 %.
- calculated creatinine clearance > or = to 60 ml/min
- bilirubin < than or = to 1.5 mg/dL, ALT < than or = to 3 x upper limit of normal unless benign congenital hyperbilirubinemia,
- pulmonary function (spirometry and corrected DLCO) > or = to 50% predicted.
- left ventricular ejection fraction > or = to 50%.
- albumin > or = to 3.0.
- Graft Criteria:
- 2 UCB units selected according to current MSKCC unit selection algorithm. High resolution 8 allele HLA typing will be performed. Unit selection will occur based on 8 allele HLA-match and CD34+ dose.
- In addition, each unit will have a cryopreserved dose of at least 1.5 x 10^7 total nucleated cells/recipient body weight (TNC/kg).
- Units with attached segments for confirmatory typing will be given preference.
Who cannot join
- Diagnosis: acute leukemia in morphologic relapse or with morphologic persistent disease (cytogenetic or molecular persistence/relapse in morphologic CR are eligible); MDS or CML or other myeloproliferative disorder with > 5% blasts; Aggressive lymphoma or HL with POD after salvage chemotherapy.
- Two prior stem cell transplants of any kind.
- One prior autologous stem cell transplant within the preceding 12 months.
- One prior allogeneic stem cell transplant within the preceding 24 months.
- Prior radiation therapy with 400cGy or more of TBI.
- Active and uncontrolled infection at time of transplantation.
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- HIV infection.
- Seropositivity for HTLV-1.
- Inadequate performance status/ organ function.
- Pregnancy or breast feeding.
- Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Reduced Intensity Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.
The traditional way of doing a donor transplant is to give high doses of chemotherapy and radiation before giving the stem cells. However, high doses of chemotherapy and radiation can have serious side-effects. The doctors think that the transplant will be safer and more likely to be successful with reduced doses of chemotherapy and radiation. The purpose of this study is to find out how good a combination of chemotherapy and radiation at reduced doses followed by a cord blood transplant are at treating cancer.
The stem cells chosen for the transplant are from umbilical cord blood. Umbilical cord blood is collected from healthy newborn babies and frozen. One cord blood collection is called a "cord blood unit." On transplant day, the cord blood will be given through the catheter just like a blood transfusion. Transplants done this way have been successful. However, this type of transplant is fairly new. Therefore, it is important to study it so the doctors can better understand how it works.
Most blood or bone marrow transplants using donor stem cells are done as part of a study. When patients are on a study we test new ways of treating them which we think may be better than the old ways. We collect information about the result of this treatment so we can understand how well the treatment works. This is so we can learn better ways to treat our patients.
- Conditions
- Leukemia, Myelodysplastic Syndrome, Non-Hodgkins Lymphoma, Chronic Myelogenous Leukemia, Hodgkins Lymphoma
- Being tested
- fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft
- Keywords
- CYCLOPHOSPHAMIDE (CYTOXAN), CYCLOSPORINE A, FLUDARABINE, G-CSF, MYCOPHENOLATE MOFETIL (MMF), THI0TEPA, UMBILICAL CORD BLOOD (UCB), 08-087
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graftDrug
Cyclophosphamide 50 mg/kg/dose x 1 IV day -6 (1 dose) Fludarabine 30 mg/m2/dose x 5 IV days -6 to -2 (5 doses) Thiotepa 5 mg/kg/dose x 2 IV days -5 to -4 (2 doses) TBI 200 cGy/dose x 2 days -2 to -1 (2 doses). On transplant day, the cord blood cells will be given through your catheter. The immune suppressing drugs you will receive are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through your catheter. Later they can be given as tablets.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | There are three chemotherapy drugs involved. They are called fludarabine (5 doses), cyclophosphamide (1 dose), and thiotepa (2 doses). Also two days of radiation therapy. This is called Total Body Irradiation or TBI. The TBI if given for two days before, the transplant. On transplant day, the cord blood cells will be given through a catheter. The immune suppressing drugs given are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through the catheter. Later they can be given as tablets. Receives: Drug: fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival/PFS at 1 Year Post UCBT.
To obtain a preliminary estimate of progression free survival at 1 year post UCBT. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 1 year post UCBT
Secondary outcomes (3)
Number of Participants With Neutrophil Recovery Post Allograft for Haplo-dCBT Recipients
Successful primary donor engraftment = neutrophill recovery within the first 45 days after transplant and partial/complete donor chimerism (>/= 10%)
Measured: up to 13 days from engraftment
Percentage of Participants With Sustained CB-derived Neutrophil Engraftment
The day 100 cumulative incidence of sustained CB-derived neutrophil engraftment.
Measured: 100 days
Percentage of Participants With Sustained CB-derived Platelet Engraftment
The day 100 cumulative incidence of sustained CB-derived platelet engraftment to >/= 20 x 10^9/L
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 posted21 Aug 2008 (estimated)
- Study start12 Aug 2008
- Primary completion15 Oct 2021
- Study completion15 Oct 2021
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Juliet Barker, MBBS, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00739141
- Sponsor's protocol ID
- 08-087
- Status last verified
- Oct 2021
- First submitted
- 19 Aug 2008
- Last updated
- 8 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ponce DM, Sauter C, Devlin S, Lubin M, Gonzales AM, Kernan NA, Scaradavou A, Giralt S, Goldberg JD, Koehne G, Perales MA, Young JW, Castro-Malaspina H, Jakubowski A, Papadopoulos EB, Barker JN. A novel reduced-intensity conditioning regimen induces a high incidence of sustained donor-derived neutrophil and platelet engraftment after double-unit cord blood transplantation. Biol Blood Marrow Transplant. 2013 May;19(5):799-803. doi: 10.1016/j.bbmt.2013.02.007. Epub 2013 Feb 14.
PubMed 23416850
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Reduced Intensity Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.
- ClinicalTrials.gov ID
- NCT00739141
- Acronym / sponsor ID
- 08-087
- Conditions
- Leukemia, Myelodysplastic Syndrome, Non-Hodgkins Lymphoma, Chronic Myelogenous Leukemia, Hodgkins Lymphoma
- Keywords
- CYCLOPHOSPHAMIDE (CYTOXAN), CYCLOSPORINE A, FLUDARABINE, G-CSF, MYCOPHENOLATE MOFETIL (MMF), THI0TEPA, UMBILICAL CORD BLOOD (UCB), 08-087
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 12 Aug 2008 (actual)
- Primary completion
- 15 Oct 2021 (actual)
- Study completion
- 15 Oct 2021 (actual)
- First posted
- 21 Aug 2008 (estimated)
- Results
- Posted 8 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The traditional way of doing a donor transplant is to give high doses of chemotherapy and radiation before giving the stem cells. However, high doses of chemotherapy and radiation can have serious side-effects. The doctors think that the transplant will be safer and more likely to be successful with reduced doses of chemotherapy and radiation. The purpose of this study is to find out how good a combination of chemotherapy and radiation at reduced doses followed by a cord blood transplant are at treating cancer.
The stem cells chosen for the transplant are from umbilical cord blood. Umbilical cord blood is collected from healthy newborn babies and frozen. One cord blood collection is called a "cord blood unit." On transplant day, the cord blood will be given through the catheter just like a blood transfusion. Transplants done this way have been successful. However, this type of transplant is fairly new. Therefore, it is important to study it so the doctors can better understand how it works.
Most blood or bone marrow transplants using donor stem cells are done as part of a study. When patients are on a study we test new ways of treating them which we think may be better than the old ways. We collect information about the result of this treatment so we can understand how well the treatment works. This is so we can learn better ways to treat our patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graftThere are three chemotherapy drugs involved. They are called fludarabine (5 doses), cyclophosphamide (1 dose), and thiotepa (2 doses). Also two days of radiation therapy. This is called Total Body Irradiation or TBI. The TBI if given for two days before, the transplant. On transplant day, the cord blood cells will be given through a catheter. The immune suppressing drugs given are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through the catheter. Later they can be given as tablets. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (59 listed)
- At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy or azacitidine or decitabine or tyrosine kinase inhibitor.
- Patients aged 18-70 years at initial referral with no available and suitably matched related or unrelated donor.
- Acute myelogenous leukemia (AML):
- Complete first remission (CR1) at high risk for relapse such as:
- Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder;
Key exclusion criteria (11 listed)
- Diagnosis: acute leukemia in morphologic relapse or with morphologic persistent disease (cytogenetic or molecular persistence/relapse in morphologic CR are eligible); MDS or CML or other myeloproliferative disorder with > 5% blasts; Aggressive lymphoma or HL with POD after salvage chemotherapy.
- Two prior stem cell transplants of any kind.
- One prior autologous stem cell transplant within the preceding 12 months.
- One prior allogeneic stem cell transplant within the preceding 24 months.
- Prior radiation therapy with 400cGy or more of TBI.
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 |
|---|---|---|
| fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graftCyclophosphamide 50 mg/kg/dose x 1 IV day -6 (1 dose) Fludarabine 30 mg/m2/dose x 5 IV days -6 to -2 (5 doses) Thiotepa 5 mg/kg/dose x 2 IV days -5 to -4 (2 doses) TBI 200 cGy/dose x 2 days -2 to -1 (2 doses). On transplant day, the cord blood cells will be given through your catheter. The immune suppressing drugs you will receive are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through your catheter. Later they can be given as tablets. | Drug | 1 |
Primary outcome
Progression Free Survival/PFS at 1 Year Post UCBT.
Time frame: 1 year post UCBT
To obtain a preliminary estimate of progression free survival at 1 year post UCBT. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
3 secondary outcomes
Number of Participants With Neutrophil Recovery Post Allograft for Haplo-dCBT Recipients
Time frame: up to 13 days from engraftment
Percentage of Participants With Sustained CB-derived Neutrophil Engraftment
Time frame: 100 days
Percentage of Participants With Sustained CB-derived Platelet Engraftment
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 8 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23416850Ponce DM, Sauter C, Devlin S, Lubin M, Gonzales AM, Kernan NA, Scaradavou A, Giralt S, Goldberg JD, Koehne G, Perales MA, Young JW, Castro-Malaspina H, Jakubowski A, Papadopoulos EB, Barker JN. A novel reduced-intensity conditioning regimen induces a high incidence of sustained donor-derived neutrophil and platelet engraftment after double-unit cord blood transplantation. Biol Blood Marrow Transplant. 2013 May;19(5):799-803. doi: 10.1016/j.bbmt.2013.02.007. Epub 2013 Feb 14.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Juliet Barker, MBBS principal investigator
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 fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft in people with Leukemia and Myelodysplastic Syndrome, 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?
The sponsor lists 59 inclusion and 11 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 8 Dec 2022. 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 8 Dec 2022). 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?
Progression Free Survival/PFS at 1 Year Post UCBT. (time frame: 1 year post UCBT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00739141, which also lists 1 linked publication.
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 8 Dec 2022.