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Acute Biphenotypic LeukemiaPhase 2NCT00719888

Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With Hematologic Disease

A Phase 2 study testing Cyclophosphamide, Cyclosporine and Double-Unit Umbilical Cord Blood Transplantation in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients with hematologic disease. Read more about this study

Who is it for?
Ages 6 months to 65 years
What is being tested?
Cyclophosphamide, Cyclosporine and Double-Unit Umbilical Cord Blood Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
135 participants
Where
3 sitesUnited States
Study dates
18 Nov 2005to 19 Dec 2024
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 6 months to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • GRAFT CRITERIA:
  • UCB units will be selected according to current umbilical cord blood graft selection algorithm; one or 2 UCB units may be used to achieve the required cell dose
  • The UCB graft is matched at 4-6 human leukocyte antigen (HLA)-A, B, DRB1 antigens with the recipient; this may include 0-2 antigen mismatches at the A or B or DRB1 loci; unit selection based on cryopreserved nucleated cell dose and HLA-A,B, DRB1 using intermediate resolution A, B antigen and DRB1 allele typing
  • If 2 UCB units are required to reach the target cell dose, each unit must be a 4-6 antigen match to the recipient
  • Age and Disease Criteria:
  • High-dose TBI regimen: 6 months to =< 45 years
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  • Middle-intensity TBI regimen: 6 months to =< 65 years
  • Conditioning regimen selection should be based on the underlying disease, presence of minimum residual disease (MRD), age, co-morbidities, and attending physician
  • Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:
  • All patients must be in complete remission (CR) as defined by hematologic recovery and < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age; patients who do not have high-risk features (for example preceding myelodysplastic syndrome [MDS], high-risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia or >= CR2) must be discussed with the principal investigator (PI) prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
  • Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the PI prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
  • Very high risk pediatric/young adult patients with acute myeloid leukemia (AML): Patients =< 25 years, however, are eligible with (M2 marrow) with =< 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately
  • Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:
  • All patients must be in CR as defined by < 5% blasts by morphology; flow cytometry in a representative bone marrow sample with cellularity >= 15% for age; patients who do not have high-risk disease (high risk CR1, greater than one cycle to obtain CR or >= CR2) must be discussed with the PI prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
  • Patients in whom adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator Ann Dahlberg prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
  • Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate
  • Advanced myelofibrosis
  • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
  • Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma (NHL) after initial therapy if stage III/IV in first partial response (PR1) or after progression if stage I/II < 1 year; stage III/IV patients are eligible after progression in CR/PR
  • Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have progressed after at least two different prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant; these patients must be presented at primary care center (PCC) prior to enrollment, given potential competing eligibility on autotransplant protocols
  • Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >= CR1 or >= PR1
  • Large cell NHL > CR2/> second partial response (PR2):
  • Patients in CR2/PR2 with initial short remission (< 6 months) are eligible
  • These patients must be presented at PCC prior to enrollment, given potential competing eligibility on autotransplant protocols
  • Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
  • Performance status score: Karnofsky (for adults) >= 70% or Eastern Cooperative Oncology Group (ECOG) 0-1 or Lansky (for children) >= 50%
  • Creatinine < 2.0 mg/dL (for adults) or creatinine clearance > 60 ml/min (for children)
  • Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
  • Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal or a pediatric patient who is unable to perform pulmonary function tests (PFTs) but has adequate pulmonary function
  • Left ventricular ejection fraction > 45% or shortening fraction > 26%

Who cannot join

  • Uncontrolled viral or bacterial infection at the time of study enrollment
  • Active or recent (prior 6 month) invasive fungal infection without interdisciplinary (ID) consult and approval
  • History of human immunodeficiency virus (HIV) infection
  • Pregnant or breastfeeding
  • Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens)
  • Patients with history of prior myeloablative transplant containing full dose TBI (greater than 8 gray [Gy]) will not be eligible for Regimen A; however, they may still enroll on Regimen B if they otherwise meet inclusion and exclusion criteria
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  • Any prior myeloablative transplant within the last 6 months
  • Patients >= 45 years: comorbidity score of 5 or higher
  • Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy are not eligible for Regimen A

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • VA Puget Sound Health Care System

    Seattle, Washington, 98101

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation or Cyclophosphamide/Fludarabine/Thiotepa/Total Body Irradiation Myeloablative Preparative Regimen

This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) works in treating patients with hematologic disease. Giving chemotherapy, such as cyclophosphamide and fludarabine, and TBI before a donor umbilical cord blood 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 cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

Read the detailed description

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I: Patients receive myeloablative conditioning comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0.

ARM II: Patients receive myeloablative conditioning comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily (QD) on days -2 and -1. Patients then undergo single- or double-unit UCBT on day 0.

Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD.

After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.

Being tested
Cyclophosphamide, Cyclosporine, Double-Unit Umbilical Cord Blood Transplantation, Fludarabine, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Burkitt Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • CyclosporineDrug

    Also called 27-400, Ciclosporin, CsA, Cyclosporin

    Given IV and PO

  • Double-Unit Umbilical Cord Blood TransplantationProcedure or surgery

    Undergo double-unit UCBT

  • FludarabineDrug

    Also called 118218, Fluorovidarabine

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV and PO

  • Total-Body IrradiationRadiation

    Also called Total Body Irradiation, Whole-Body Irradiation, SCT_TBI, TBI

    Undergo high-dose or moderate-intensity TBI

  • Umbilical Cord Blood TransplantationProcedure or surgery

    Also called Cord Blood Transplantation, UCB transplantation

    Undergo UCBT

  • ThiotepaDrug

    Also called 1,1',1"-phosphinothioylidynetrisaziridine, 1,1',1''-Phosphinothioyldynetrisaziridine, 52-24-4, 6396

    Given IV

Study groups in NCT00719888
Study groupRoleWhat they receive
Treatment (myeloablative UCBT)ExperimentalPatients receive myeloablative conditioning comprising fludarabine IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI BID on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine PO (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) TID on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD.
Receives: Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Double-Unit Umbilical Cord Blood Transplantation; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation
Arm II (myeloablative UCBT)ExperimentalPatients receive myeloablative conditioning comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI QD on days -2 and -1. Patients then undergo single- or double-unit UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine PO (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) TID on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD.
Receives: Drug: Cyclophosphamide; Drug: Cyclosporine; Procedure: Double-Unit Umbilical Cord Blood Transplantation; Drug: Fludarabine; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation; Drug: Thiotepa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Overall survival defined as patient being alive at 1 year post-transplant. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: 1 year post-transplant

Secondary outcomes (9)

  1. Change in Level of Chimerism at Multiple Time Points

    Peripheral blood chimerism studies (sorted for CD3, CD14, CD33, CD56 cells) were collected for all UCBT recipients for days 28, 56, 80, 365, and 730 post-transplant. The combined median of the percent donor, along with full range, is captured to show change in level of chimerism at multiple time points up to 2 years post-transplant. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: Baseline up to 2 years post-transplant

  2. Incidence of Transplant-related Mortality (TRM)

    Defined as death due to complication (other than relapse) within 6 months following UCBT. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: At 6 months post-transplant

  3. Neutrophil Engraftment

    Neutrophil engraftment after UCBT is defined as the first day of absolute neutrophil count (ANC) ≥ 5 x 10⁸/L for 3 consecutive measures. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: Up to day 42 post-transplant

  4. Platelet Engraftment

    Platelet (PLT) engraftment after UCBT is defined as the first day of platelet count > 20,000/μl without subsequent transfusions for 7 days. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: Up to 6 months post-transplant

  5. Event of Grade II-IV and III-IV Acute Graft-versus-host Disease (aGVHD)

    Each event of aGVHD will be assigned an overall aGVHD score based on extent of skin rash, volume of diarrhea, and maximum bilirubin level, per protocol Appendix I, "GVHD Staging and Grading." Scores reported range from most mild at 2, to worse at 4. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: Up to day 100 post-transplant

  6. Event of Chronic Graft-verses-host-disease (cGVHD)

    Each event of cGVHD level will be assessed overall as either 'Limited' (mild and with single organ involvement) or 'Extensive' (involvement of two or more organs with symptoms) based on extent of skin rash, volume of diarrhea, and maximum bilirubin level, per protocol Appendix I, "GVHD Staging and Grading." Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: Up to 2 years post-transplant

  7. Event of Clinically Significant Infections

    Each event of infection will be assessed to determine whether or not it is clinically significant. An infection is defined as clinically significant when it is scored as ≥ grade 3 (where worse outcomes are associated with higher grading) in accordance with the CTCAE version 3.0/protocol Appendix VI, and constitutes a Serious Adverse Event (SAE). Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: Up to 2 years post-transplant

  8. Incidence of Relapse

    Relapse is defined as post-transplant disease recurrence in participants who had initially recovered or improved, with incidence measured from Day 0 to 1 year post-transplant, and from 1 year post-transplant to 2 years post-transplant. Monitoring will take place separately for the single and double UCBT cohorts.

    Measured: At 1 and 2 years post-transplant

  9. Progression-free Survival (PFS)

    PFS is defined as the time (in days) from UCBT until the disease progresses or the patient dies from any cause, with incidence measured up to 2 years post-transplant. Monitoring will take place separately for the single and double UCBT cohorts. Measure will be reported as the median amount of days from full minimum and maximum range.

    Measured: Up to 2 years post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jul 2008 (estimated)
  2. Study start18 Nov 2005
  3. Primary completion22 Dec 2023
  4. Study completion19 Dec 2024

Resources

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
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00719888
Sponsor's protocol ID
2010.00
Other IDs
NCI-2010-00190, 2010, RG2807002
Status last verified
Mar 2025
First submitted
19 Jul 2008
Last updated
7 Mar 2025
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Colgan JN, Gooley TA, Pedersen JB, Hadland B, Summers C, Carpenter PA, Delaney CC, Milano F, Dahlberg A. Prospective phase 2 trial of high- and intermediate-intensity myeloablative conditioning for cord blood transplantation. Blood Adv. 2026 Oct 21:bloodadvances.2026021974. doi: 10.1182/bloodadvances.2026021974. Online ahead of print.

    PubMed 42907159

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Cyclosporine and Double-Unit Umbilical Cord Blood Transplantation in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 3 sites 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 30 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 7 Mar 2025). 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?

Overall Survival (time frame: 1 year post-transplant). 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 NCT00719888, 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 7 Mar 2025.

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