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Acute LeukemiaPhase 2NCT02722668

UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep

A Phase 2 study testing Fludarabine, Cyclophosphamide and MMF in people with Acute Leukemia and Acute Myeloid Leukemia, run by Masonic Cancer Center, University of Minnesota 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 is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Read more about this study

Who is it for?
Ages Up to 75 years
What is being tested?
Fludarabine, Cyclophosphamide and MMF
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
15 May 2017to 22 Feb 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 Up to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age, Performance Status, and Graft Criteria
  • <70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)
  • Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
  • UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
  • Eligible Diseases All diseases listed below are advanced hematologic malignancies not curable by conventional chemotherapy. Responses to conventional treatment range from zero to 30% but are typically short lived.
  • Acute Leukemias: Must be in remission by morphology (<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
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  • Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients > 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk. Favorable risk AML is defined as having one of the following:
  • t(8,21) without cKIT mutation
  • inv(16) or t(16;16) without cKIT mutation
  • Normal karyotype with mutated NPM1 and wild type FLT-ITD
  • Normal karyotype with double mutated CEBPA
  • Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation
  • Acute lymphoblastic leukemia (ALL)/lymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL. High risk ALL is defined as having one of the following:
  • Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1
  • 30 years of age or older at diagnosis
  • White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL) at diagnosis
  • CNS leukemia involvement during the course of disease
  • Slow cytologic response (>10% lymphoblasts in bone marrow on Day 14 of induction therapy)
  • Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy
  • Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR
  • Chronic myelogenous leukemia in chronic or accelerated phase, or CML blast crisis in morphological remission (<5% blasts): Chronic phase patients must have failed at least two tyrosine kinase inhibitors, been intolerant to all available TKIs, or have T315I mutation.
  • Myelodysplastic syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by bone marrow aspirate morphology. If ≥5% blasts, patient requires chemotherapy for cytoreduction to <5% blasts prior to transplantation.
  • MRD positive leukemia (AML, ALL or accelerated/blast phase CML). Selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status.
  • Leukemia or MDS in aplasia. These patients may be taken to transplant if after induction therapy they remain with aplastic bone marrow and no morphological or flow-cytometry evidence of disease ≥ 28 days post-therapy. These high risk patients will be analyzed separately.
  • Burkitt's lymphoma in CR2 or subsequent CR
  • Relapsed T-Cell Lymphoma that is chemotherapy sensitive in CR/PR that has failed or ineligible for an autologous transplant.
  • Natural killer cell malignancies
  • Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease who are ineligible for an autologous transplant.
  • Relapsed Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless bulky disease and an estimated tumor doubling time of less than one month.
  • Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
  • Relapsed Multiple Myeloma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant.
  • Plasma Cell Leukemia after initial therapy if achieved at least in partial remission; or relapsed and achieved subsequent remission (CR/PR)
  • Acquired Bone marrow failure syndromes, except for Fanconi anemia
  • Myeloproliferative Neoplasms/Myelofibrosis
  • Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.
  • Additional Criteria for Bulky Disease (lymphomas)
  • If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately)
  • If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
  • Organ Function Criteria
  • Adequate organ function is defined as:
  • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 40%. For children that are not able to cooperate with MUGA and echocardiography, such should be clearly stated in the physician's note.
  • Pulmonary: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
  • Liver: Transaminases ≤ 5 x upper limit of normal (ULN) and total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis
  • Renal: Creatinine ≤ 2.0 mg/dl (adults) and creatinine clearance ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated creatinine clearance ≥ 40 ml/min/1.73m^2. Adequate performance status is defined as Karnofsky score ≥ 70% (≥ 16 years of age) or Lansky score ≥ 50 (pediatrics)
  • Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
  • Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)

Who cannot join

  • Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
  • Untreated active infection
  • Active HIV infection or known HIV positive serology
  • Less than 3 months since prior myeloablative transplant
  • Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
  • CML in blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
  • Active central nervous system malignancy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen

This is a phase II trial using a non-myeloablative cyclophosphamide/ fludarabine/total body irradiation (TBI) preparative regimen with modifications based on factors including diagnosis, disease status, and prior treatment. Single or double unit selected according to current University of Minnesota umbilical cord blood graft selection algorithm.

Being tested
Fludarabine, Cyclophosphamide, MMF, Sirolimus, TBI
Keywords
AML, ALL, CML, CLL, SLL
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Myelodysplastic Syndromes, Dendritic Cell Sarcoma, Interdigitating, Hodgkin Disease, Multiple Myeloma

What participants receive

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

  • FludarabineDrug

    Also called Fludara

    Both Arms: 30 mg/m^2 IV over 1 hour Day -6 to Day -2

  • CyclophosphamideDrug

    Also called Cytoxan

    Arm 1: 50 mg/kg IV over 2 hours Day -6

  • MMFDrug

    Also called Mycophenolate Mofetil

    Both Arms:

    Mycophenolate mofetil (MMF) 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. In obese patients (>125% IBW) 15 mg/kg every 12 hours may be considered. Pediatric patient (<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning Day -3. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. Patients will be eligible for MMF dosing and pharmacokinetics studies.

    Stop MMF at Day +30 or 7 days after engraftment, whichever day is later, if no acute graft versus host disease (GVHD). (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count [ANC) ≥ 0.5 x 109 /L]). If no donor engraftment, do not stop MMF.

  • SirolimusDrug

    Also called Rapamycin

    Both Arms:

    Adult Dosing: Sirolimus will be administered starting at Day -3 with 8-12 mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL by high-performance liquid chromatography (HPLC) and will be monitored per institutional guidelines. In the absence of acute GVHD sirolimus may be tapered starting at Day +100 and eliminated by Day +180 post-transplantation.

    Pediatric Dosing: Sirolimus will be administered starting on Day -3 with an oral loading dose of 10 mg followed by maintenance dosing of 2.5 mg/m^2/day (Maximum total daily dose of 4mg) as per institutional guidelines. Target serum concentration goals are 3 to 12 mg/mL by high-performance liquid chromatography (HPLC) and will be monitored per institutional guidelines.

  • TBIRadiation

    Also called Total body irradiation

    Both Arms: 200 cGy on Day -1

  • Umbilical cord blood cell infusionBiological

    Also called UCB

    Both Arms: Day 0

  • ATGBiological

    Also called Anti-thymocyte Globulin

    Arm 2: 15 mg/kg IV every 12 hours Day -6 to Day -4

Study groups in NCT02722668
Study groupRoleWhat they receive
No Anti-thymocyte Globulin (ATG)ExperimentalHematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycles of multi-agent chemotherapy within the 3 months previous to umbilical cord blood transplantation.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MMF; Drug: Sirolimus; Radiation: TBI; Biological: Umbilical cord blood cell infusion
Anti-thymocyte Globulin (ATG)ExperimentalHematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplantation, should receive Anti-thymocyte Globulin (ATG) as part of their conditioning regimen.
Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MMF; Drug: Sirolimus; Radiation: TBI; Biological: Umbilical cord blood cell infusion; Biological: ATG

What is being measured

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

  1. Probability of Acute Graft Versus Host Disease (GVHD)

    Simple proportions will be used to estimate the probability of grade II-IV actue GVHD.

    Measured: Day 100

Secondary outcomes (7)

  1. Incidence of Acute GVHD

    Percentage of patients with grade III-IV acute GVHD.

    Measured: Day 100

  2. Transplant Related Mortality

    Measured: 6 months post transplant

  3. Chimerism

    Percentage of subjects with donor chimerism.

    Measured: Day 21

  4. Chimerism

    Percentage of subjects with donor chimerism.

    Measured: Day 100

  5. Chimerism

    Percentage of subjects with donor chimerism.

    Measured: Day 180

  6. Chimerism

    Percentage of subjects with donor chimerism.

    Measured: 1 year post transplant

  7. Neutrophil Engraftment

    Percentage of subjects with neutrophil engraftment.

    Measured: 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 posted30 Mar 2016 (estimated)
  2. Study start15 May 2017
  3. Primary completion22 Feb 2023
  4. Study completion22 Feb 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
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02722668
Sponsor's protocol ID
2015LS149
Other IDs
MT2015-17
Status last verified
Jun 2025
First submitted
24 Mar 2016
Last updated
4 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Cyclophosphamide and MMF in people with Acute Leukemia and Acute Myeloid Leukemia, run by Masonic Cancer Center, University of Minnesota 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 46 inclusion and 8 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 4 Jul 2025. 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 4 Jul 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?

Probability of Acute Graft Versus Host Disease (GVHD) (time frame: Day 100). 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 NCT02722668.

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 4 Jul 2025.

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