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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1NCT00343798

A Pilot Study to Evaluate the Co-Infusion of Ex Vivo Expanded Cord Blood Cells With an Unmanipulated Cord Blood Unit in Patients Undergoing Cord Blood Transplant for Hematologic Malignancies

A Phase 1 study testing cyclophosphamide, fludarabine phosphate and cyclosporine in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, run by Fred Hutchinson Cancer Center at 4 sites in United States.

Completed

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

Official record
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Trial summary

This phase I multicenter feasibility trial is studying the safety and potential efficacy of infusing ex vivo expanded cord blood progenitors with one unmanipulated umbilical cord blood unit for transplantation following conditioning with fludarabine, cyclophosphamide and total body irradiation (TBI), and… Read more about this study

Who is it for?
Ages 6 months to 45 years
What is being tested?
cyclophosphamide, fludarabine phosphate and cyclosporine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
4 sitesUnited States
Study dates
Apr 2006to Jul 2013
Phase
Phase 1
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 6 months to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patient has no existing 0-1 HLA-A, B, C, DRB1 and DQB1 matched related donor
  • Acute Myeloid Leukemia:
  • High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or HR as defined by referring institution treatment protocol), >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2);
  • All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%;
  • Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry (< 5% blasts) and, recovery of peripheral blood counts with no circulating blasts, may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
  • Acute lymphoblastic leukemia:
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  • High risk CR1 (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia (MLL) rearrangements, hypodiploid);
  • > 1 cycle to obtain CR;
  • >= CR2;
  • All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%;
  • Patients in which adequate marrow/biopsy specimens can not be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry (< 5% blasts) and, recovery of peripheral blood counts with no circulating blasts, may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
  • Chronic Myelogenous Leukemia:
  • Patients in blast crisis (BC) must receive therapy and must achieve accelerated phase (AP)/chronic phase (CP) in order to be eligible (patients who remain in BC are not eligible);
  • If in first chronic phase, patient must have failed or be intolerant to imatinib mesylate
  • Myelodysplasia (MDS):
  • International Prognostic Scoring System (IPSS) Int-2 or high risk (Refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics;
  • Blasts must be < 10% morphologically in representative bone marrow aspirate (obtained < 2 weeks from enrollment)
  • Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma (NHL) after initial therapy if stage III/IV in first partial remission (PR1) or after progression if stage I/II < 1 year; Stage III/IV patients are eligible after progression in complete response (CR)/partial response (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 Patient Care Conference [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/ > 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
  • Serum creatinine =< 2.0 mg/dL (adults) and creatinine clearance > 60 ml/min (pediatrics)
  • 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
  • Diffusing capacity of the lung for carbon monoxide corrected (DLCOcorr) > 50% normal
  • Left ventricular ejection fraction >= 45% or shortening fraction > 26%
  • Karnofsky score >= 70% (adults) or Lansky score >= 50% (pediatrics)

Who cannot join

  • Acute leukemia in relapse (>= 5% marrow blasts by morphology)
  • Active central nervous system (CNS) leukemia involvement at the time of study enrollment (cerebrospinal fluid with > 5 white blood cells (WBC)/mm^3 AND malignant cells on cytospin)
  • Chemotherapy refractory large cell lymphoma and high grade NHL (progressive disease after > 2 salvage regimens)
  • Female patients who are pregnant or breastfeeding
  • Karnofsky performance status < 70% (adults) or Lanksy score < 50% (pediatrics)
  • Prior autologous or allogeneic stem cell transplant with myeloablative preparative regimen (If =< 18 years old, prior myeloablative transplant within the last 6 months)
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  • Uncontrolled viral, or bacterial infection at the time of study enrollment
  • Active or recent (prior 6 months) invasive fungal infection without ID consult and approval
  • Seropositive for human immunodeficiency virus (HIV)
  • Consenting 5 of 6 or 6 of 6 HLA-matched related donor available
  • Unable to provide informed consent
  • Use of any other experimental drug within 28 days of baseline

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • University of Colorado

    Denver, Colorado, 80217-3364

  • City of Hope Medical Center

    Duarte, California, 91010

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors With an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies

This phase I multicenter feasibility trial is studying the safety and potential efficacy of infusing ex vivo expanded cord blood progenitors with one unmanipulated umbilical cord blood unit for transplantation following conditioning with fludarabine, cyclophosphamide and total body irradiation (TBI), and immunosuppression with cyclosporine and mycophenolate mofetil (MMF) for patients with hematologic malignancies. Chemotherapy, such as fludarabine and cyclophosphamide, and TBI given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts are more likely to recover more quickly if increased numbers of cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one unexpanded cord blood unit is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two cord blood units makes up the patient's new blood system, and how quickly immune system cells return

Read the detailed description

PRIMARY OBJECTIVES:

  1. Examine the safety and toxicity when ex vivo expanded cord blood cells are co-infused with a second non-human leukocyte antigen (HLA)-identical cord blood graft following myeloablative therapy in patients with hematologic malignancies.

II. Examine the in vivo persistence of the ex vivo expanded cord blood cells. The kinetics and durability of hematopoietic reconstitution (time to engraftment defined as the first of 2 consecutive days in which the absolute neutrophil count [ANC] > 500) will be determined and the relative contribution to engraftment of the expanded cord blood cells and the unmanipulated cord blood cells in early and long-term engraftment will be determined by donor chimerisms.

SECONDARY OBJECTIVES:

  1. Estimate the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients receiving Notch-expanded cord blood cells.

II. Estimate the incidence of transplant related mortality at day 100.

III. Estimate the incidence of malignant relapse and probabilities of overall and event-free survival at 1 and 2 years post transplant.

IV. Obtain preliminary data on the phenotype and function of immune cells recovering in patients receiving expanded and unmanipulated cord blood grafts.

  1. Obtain feasibility data on overnight shipment of ex vivo expanded progenitor cells for infusion in patients are distant sites.

OUTLINE:

MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI twice daily (BID) on days -4 to -1.

TRANSPLANTATION : On Day 0, patients undergo double-unit umbilical cord blood transplantation which includes the infusion of one unmanipulated (not expanded) cord blood unit followed 4 hours later by infusion of one ex vivo-expanded cord blood unit.

GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS: Patients initially receive cyclosporine IV beginning on day -3. Cyclosporine may be given orally when the patient can tolerate oral medications and has a normal gastrointestinal transit time. Cyclosporine is given until day 100, and may taper on day 101 if there is no graft versus host disease. Patients also receive MMF IV on days -3 to 5 and then may receive oral MMF beginning day 6 to 30. MMF is stopped at Day 30 or 7 days after engraftment, whichever day is later, if no acute GVHD.

After completion of study treatment, patients are followed up periodically for 2 years.

Being tested
cyclophosphamide, fludarabine phosphate, cyclosporine, mycophenolate mofetil, ex-vivo umbilical cord blood expansion
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Leukemia, Myeloid, Chronic-Phase, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given IV

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given IV or PO

  • ex-vivo umbilical cord blood expansionOther

    Undergo double-unit umbilical cord blood transplantation

  • double-unit umbilical cord blood transplantationProcedure or surgery

    Undergo double-unit umbilical cord blood transplantation

  • biopsyProcedure or surgery

    Also called biopsies

    Optional correlative studies

  • immunologic techniqueOther

    Also called immunological laboratory methods, laboratory methods, immunological

    Correlative studies

  • diagnostic laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00343798
Study groupRoleWhat they receive
Treatment (umbilical cord blood transplant)ExperimentalMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. TRANSPLANTATION : Patients undergo double-unit umbilical cord blood transplantation comprising unmanipulated umbilical cord blood unit IV over 20-30 minutes, and 4-6 hours later patients receive ex vivo-expanded umbilical cord blood cells IV over 30 minutes on day 0. GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS: Patients receive cyclosporine IV every 8 or 12 hours on days -3 to 100, followed by a taper to at least day 180. Patients also receive MMF IV every 8 hours on days -3 to 5 and then PO, if tolerated, on days 6-30.
Receives: Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: ex-vivo umbilical cord blood expansion; Procedure: double-unit umbilical cord blood transplantation; Procedure: biopsy; Other: immunologic technique; Other: diagnostic laboratory biomarker analysis

What is being measured

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

  1. Severe (grades 3 and 4) acute GVHD

    Measured: Up to day 100

  2. Grade greater than or equal to 3 infusional toxicity

    Measured: Day 0

  3. Graft failure as defined by failure to achieve ANC greater than or equal to 500/mm^3 of donor origin

    Measured: By day +42

Timeline

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

  1. First posted23 Jun 2006 (estimated)
  2. Study startApr 2006
  3. Primary completionJul 2013

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00343798
Sponsor's protocol ID
2044.00
Other IDs
NCI-2010-00236, R43HL106868, R24HL074445, RC2HL101844
Status last verified
Feb 2015
First submitted
22 Jun 2006
Last updated
11 Feb 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cyclophosphamide, fludarabine phosphate and cyclosporine in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, run by Fred Hutchinson Cancer Center at 4 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 29 inclusion and 12 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 11 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Severe (grades 3 and 4) acute GVHD (time frame: Up to day 100). The study lists 3 primary outcomes in all. 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 NCT00343798.

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 11 Feb 2015.

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