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Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT01175785

Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies

A Phase 2 study testing umbilical cord blood transplantation, fludarabine phosphate and cyclophosphamide in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Myeloid Leukemia in Remission, run by Nohla Therapeutics, Inc. at 1 site 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 II trial is studying the safety and potential efficacy of infusing non-human leukocyte antigen matched ex vivo expanded cord blood progenitors with one or two unmanipulated umbilical cord blood units for transplantation following conditioning with fludarabine phosphate, cyclophosphamide and total body… Read more about this study

Who is it for?
Ages 6 months to 45 years
What is being tested?
umbilical cord blood transplantation, fludarabine phosphate and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Aug 2010to Aug 2014
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 6 months to 45 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Acute myeloid leukemia:
  • High risk complete response (CR)1 as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or as defined by referring institution treatment protocol), >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; >= 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, 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, Colleen Delaney prior to enrollment
  • Acute lymphoblastic leukemia:
  • 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]
Show all 22Show fewer
  • Greater than 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 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, Colleen Delaney prior to enrollment
  • 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
  • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate 2 (Int-2) or high risk (i.e., refractory anemia with excess myeloblasts [RAEB], refractory anemia with excess blasts in transformation [RAEB-T]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
  • Karnofsky (>= 16 years old) >= 70%
  • Lansky (< 16 years old) >= 50%
  • Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL (adults)
  • Calculated creatinine clearance must be > 60 mL/min (children < 18 years old)
  • Total serum bilirubin must be < 3 mg/dl
  • Transaminases must be < 3 x the upper limit of normal
  • Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 50% normal
  • For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air
  • Left ventricular ejection fraction > 45% OR shortening fraction > 26%
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Uncontrolled viral or bacterial infection at the time of study enrollment
  • Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
  • History of human immunodeficiency virus (HIV) infection
  • Pregnant or breastfeeding
  • If =< 18 years old, prior myeloablative transplant within the last 6 months
  • If > 18 years old prior myeloablative allotransplant or autologous transplant
  • Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells to Augment Single or Double Myeloablative Cord Blood Transplantation in Patients With Hematologic Malignancies

This phase II trial is studying the safety and potential efficacy of infusing non-human leukocyte antigen matched ex vivo expanded cord blood progenitors with one or two unmanipulated umbilical cord blood units for transplantation following conditioning with fludarabine phosphate, cyclophosphamide and total body irradiation, and immunosuppression with cyclosporine and mycophenolate mofetil for patients with hematologic malignancies. Chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation 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 recover more quickly when more 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 or two unexpanded cord blood units 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 or three 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 infused as an off-the-shelf non-human leukocyte antigen (HLA) matched product with the goal of providing rapid but transient myelopoiesis in the setting of a single or double umbilical cord blood transplant.

II. Examine the in vivo persistence of the ex vivo expanded cord blood product. The kinetics and durability of hematopoietic reconstitution will be determined and the relative contribution to engraftment of the expanded cord blood product and the unmanipulated cord blood unit(s) in early and long-term engraftment will be determined by frequent determination of donor chimerisms in the peripheral blood.

SECONDARY OBJECTIVES

  1. Estimate the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients receiving off-the-shelf ex vivo expanded and cryopreserved 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 incidence of infections/viral reactivation from the start of conditioning to 100 days post transplant and then at 6 months, 1 year and 2 years post transplant as possible.

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

VI. Examination of possible immunologic factors leading to emergence of a dominant unit.

OUTLINE:

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

TRANSPLANTATION: Patients undergo unmanipulated single- or double-unit umbilical cord blood transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4 hours following the last unmanipulated cord blood infusion.

GVHD PROPHYLAXIS: Patients initially receive cyclosporine (CSP) IV over 1 hour beginning on day -3. CSP may be given orally (PO) when the patient can tolerate oral medications and has a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101 if there is no graft versus host disease. Patients also receive mycophenolate mofetil (MMF) IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is continued for a minimum of 30 days or until 7 days after blood counts recover whichever is later. If there is no evidence of acute GVHD and donor cluster of differentiation (CD)3 engraftment is at least 50% from one donor MMF may be tapered.

Being tested
umbilical cord blood transplantation, fludarabine phosphate, cyclophosphamide, ex vivo-expanded cord blood progenitor cell infusion, total-body irradiation
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Congenital Abnormalities, Leukemia, Myeloid, Chronic-Phase, Anemia, Refractory, Anemia, Refractory, with Excess of Blasts

What participants receive

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

  • umbilical cord blood transplantationProcedure or surgery

    Also called cord blood transplantation, transplantation, umbilical cord blood, UCB transplantation

    Undergo unmanipulated umbilical cord blood transplant

  • fludarabine phosphateDrug

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

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • ex vivo-expanded cord blood progenitor cell infusionBiological

    Also called Dilanubicel, NLA101

    Undergo ex-vivo expanded cryopreserved cord blood progenitor cells

  • total-body irradiationRadiation

    Also called TBI

    Undergo TBI

  • cyclosporineDrug

    Also called ciclosporin, cyclosporin, cyclosporin A, CYSP

    Given IV

  • mycophenolate mofetilDrug

    Also called Cellcept, MMF

    Given IV and PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01175785
Study groupRoleWhat they receive
Treatment (chemo, radiation, transplant, GVHD prophylaxis)ExperimentalPatients receive fludarabine phosphate IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI twice daily on days -4 to -1. Patients undergo unmanipulated single- or double-unit umbilical cord blood transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4 hours following the last unmanipulated cord blood infusion. Patients initially receive CSP IV over 1 hour beginning on day -3. CSP may be given PO when the patient can tolerate oral medications and has a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101 if there is no graft versus host disease. Patients also receive MMF IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is continued for a minimum of 30 days or until 7 days after blood counts recover whichever is later. If there is no evidence of acute GVHD and donor CD3 engraftment is at least 50% from one donor MMF may be tapered.
Receives: Procedure: umbilical cord blood transplantation; Drug: fludarabine phosphate; Drug: cyclophosphamide; Biological: ex vivo-expanded cord blood progenitor cell infusion; Radiation: total-body irradiation; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: laboratory biomarker analysis

What is being measured

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

  1. Time to neutrophil engraftment

    Defined as the first of 2 consecutive days in which the absolute neutrophil count (ANC) >= 500.

    Measured: By day 42

  2. Time to platelet engraftment

    Measured: By day 100

  3. Overall survival

    Measured: Day 100

  4. Overall survival

    Measured: Day 180

  5. Overall survival

    Measured: 1 year

  6. Overall survival

    Measured: 2 years

  7. Event-free survival

    Measured: Day 100

  8. Event-free survival

    Measured: Day 180

  9. Event-free survival

    Measured: 1 year

  10. Event-free survival

    Measured: 2 years

  11. Incidence of severe (grades 3-4) acute GVHD

    Measured: Up to day 100

  12. Incidence of grade greater than or equal to 3 infusional toxicity

    Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

    Measured: By day 100

  13. Primary graft failure

    Defined as failure to achieve ANC >= 500/mm^3 of donor origin.

    Measured: By day 42

  14. Secondary graft failure

    Measured: Up to 2 years

Timeline

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

  1. First posted5 Aug 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionAug 2014
  4. Study completionAug 2014

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01175785
Sponsor's protocol ID
2378.00
Other IDs
NCI-2010-01426, 2378, 2378.00, P30CA015704, RC2HL101844
Status last verified
Feb 2019
First submitted
3 Aug 2010
Last updated
5 Mar 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Milano F, Thur LA, Blake J, Delaney C. Infusion of Non-HLA-Matched Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitors in Patients Undergoing Cord Blood Transplantation: Result of a Phase II Clinical Trial. Front Cell Dev Biol. 2022 Apr 4;10:835793. doi: 10.3389/fcell.2022.835793. eCollection 2022.

    PubMed 35445027

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing umbilical cord blood transplantation, fludarabine phosphate and cyclophosphamide in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Myeloid Leukemia in Remission, run by Nohla Therapeutics, Inc. 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 22 inclusion and 7 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 5 Mar 2019. 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?

Time to neutrophil engraftment (time frame: By day 42). The study lists 14 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 NCT01175785, 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 5 Mar 2019.

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