Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases

NCT ID: NCT01962636

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-31

Study Completion Date

2027-02-28

Brief Summary

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This is a treatment guideline for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI).

Detailed Description

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This is a study to collect routine clinical data from UCBT using unrelated single or double UCB units as an alternative, non-HLA-matched stem cell source for patients with hematological diseases.

* data collection from transplant preparative therapy consisting of treatments with chemotherapeutic regimens and total body irradiation.
* data collection from umbilical cord blood selection and infusion.
* data collection from standard supportive disease and transplant related care.

Pre- and post-transplant medication, UCB selection and infusion, supportive care, and follow-up will be according to the current University of Minnesota BMT guidelines.

An average of 18 patients are expected to be treated on this protocol per year.

Conditions

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Acute Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL) Chronic Myelogenous Leukemia Plasma Cell Leukemia Myelofibrosis Myelodysplasia Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Marginal Zone B-Cell Lymphoma Follicular Lymphoma Lymphoplasmacytic Lymphoma Mantle-Cell Lymphoma Prolymphocytic Leukemia Diffuse Large B Cell Lymphoma Lymphoblastic Lymphoma Burkitt's Lymphoma Non-Hodgkin Lymphoma Multiple Myeloma

Keywords

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Umbilical Cord Transplant Acute Myeloid Leukemia (AML) Acute Lymphocytic Leukemia (ALL) Chronic Myelogenous Leukemia Plasma Cell Leukemia Myelofibrosis Myelodysplasia Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Marginal Zone B-Cell Lymphoma Follicular Lymphoma Lymphoplasmacytic Lymphoma Mantle-Cell Lymphoma Prolymphocytic Leukemia Large Cell Non-Hodgkin Lymphoma Lymphoblastic Lymphoma Burkitt's Lymphoma Non-Hodgkin Lymphoma Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Umbilical Cord Blood Transplant

The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

25 mg/m\^2 IV of Fludarabine will be given over 1 hour on days -8, -7, and -6 pre-UCB transplant.

Cyclophosphamide

Intervention Type DRUG

60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.

Total Body Irradiation

Intervention Type RADIATION

165 cGy of total body irradiation will be given twice a day on days -4, -3, -2, and -1.

Cyclosporine A

Intervention Type DRUG

Cyclosporine A (CSA) will start day -3 and will be administered PO/IV maintaining a trough level between 200 and 400 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.

Mycophenylate mofetil

Intervention Type DRUG

Mycophenylate mofetil (MMF) 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3.

Umbilical cord blood

Intervention Type BIOLOGICAL

Pre-medications and UCB infusion will be per current institutional policies/guidelines. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. If 2 units are used, both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending or designee.

Interventions

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Fludarabine

25 mg/m\^2 IV of Fludarabine will be given over 1 hour on days -8, -7, and -6 pre-UCB transplant.

Intervention Type DRUG

Cyclophosphamide

60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.

Intervention Type DRUG

Total Body Irradiation

165 cGy of total body irradiation will be given twice a day on days -4, -3, -2, and -1.

Intervention Type RADIATION

Cyclosporine A

Cyclosporine A (CSA) will start day -3 and will be administered PO/IV maintaining a trough level between 200 and 400 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.

Intervention Type DRUG

Mycophenylate mofetil

Mycophenylate mofetil (MMF) 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3.

Intervention Type DRUG

Umbilical cord blood

Pre-medications and UCB infusion will be per current institutional policies/guidelines. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. If 2 units are used, both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending or designee.

Intervention Type BIOLOGICAL

Other Intervention Names

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Fludara Cytoxan CSA MMF UCB

Eligibility Criteria

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Inclusion Criteria

* Eligible Disease Status

* Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
* Very high risk pediatric patients with AML: Patients \<21 years, however, are eligible with (M2 marrow) with \< 25% blasts in marrow after having failed one or more cycles of chemotherapy.
* Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index \< 0.81, \> 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
* Very high risk pediatric patients with ALL: patients \<21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
* 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.
* Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
* Advanced Myelofibrosis
* Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be \< 10% by a representative bone marrow aspirate morphology.
* Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression/relapse within 12 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 (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
* Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are 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.
* Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II \< 1 year.
* Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin \> 3 mg/L, may be considered for this protocol after initial therapy.
* Myeloproliferative Syndromes
* Availability of suitable UCB unit(s)
* 0 to 55 years
* Voluntary written consent (adult or parental/guardian)

Exclusion Criteria

* previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
* chemotherapy refractory large cell and high grade NHL (ie progressive disease after \> 2 salvage regimens)
* 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
* pregnant or breastfeeding
* HIV positive
Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claudio Brunstein, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Claudio Brunstein, MD

Role: CONTACT

Phone: 612-625-3918

Email: [email protected]

Facility Contacts

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Claudio Brunstein, MD

Role: primary

Other Identifiers

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2013OC013

Identifier Type: -

Identifier Source: org_study_id