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Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

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ClinicalTrials.gov Identifier: NCT01690520
Recruitment Status : Active, not recruiting
First Posted : September 21, 2012
Last Update Posted : June 12, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Nohla Therapeutics, Inc.

Brief Summary:
This randomized phase II trial studies how well donor umbilical cord blood transplant with or without ex-vivo expanded cord blood progenitor cells works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy stem cells and ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded cord blood progenitor cells is more effective than giving a donor umbilical cord blood transplant alone.

Condition or disease Intervention/treatment Phase
Acute Biphenotypic Leukemia Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia in Remission Chronic Myelogenous Leukemia Myelodysplastic Syndrome Drug: Cyclophosphamide Drug: Cyclosporine Biological: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion Drug: Fludarabine Phosphate Drug: Mycophenolate Mofetil Drug: Thiotepa Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare the time to neutrophil engraftment (absolute neutrophil count [ANC] >= 500) in patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not receive the product.

SECONDARY OBJECTIVES:

I. Provide initial data on clinical and economic benefit, such as time to platelet engraftment, duration of initial hospitalization, transplant-related mortality (TRM), death without engraftment, and incidence of severe infections in the first 100 days post-transplant.

II. The kinetics of immune system recovery will also be evaluated in both arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Standard of Care Arm:

CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose total-body irradiation (TBI) twice daily (BID) on days -4 to -1 OR, patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI once daily (QD) on days -2 to -1.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood (UCB) transplant on day 0.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or thrice daily (TID) (children) or orally (PO) on days -3 to 100 with taper beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

Experimental Arm:

CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4 hours after completion of UCB transplant.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.

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


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-Center, Open-Label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-The-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells in Patients With Hematologic Malignancies
Actual Study Start Date : December 11, 2012
Estimated Primary Completion Date : October 31, 2018


Arm Intervention/treatment
Active Comparator: Arm I (standard of care)

CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.

Drug: Cyclophosphamide
Given IV

Drug: Cyclosporine
Given IV or PO

Drug: Fludarabine Phosphate
Given IV

Drug: Mycophenolate Mofetil
Given IV or PO

Drug: Thiotepa
Given IV

Radiation: Total-Body Irradiation
Undergo high dose or middle intensity TBI

Procedure: Umbilical Cord Blood Transplantation
Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation

Experimental: Arm II (experimental)

CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.

TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.

GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.

Drug: Cyclophosphamide
Given IV

Drug: Cyclosporine
Given IV or PO

Biological: Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion
Given IV
Other Names:
  • NLA101
  • Dilanubicel

Drug: Fludarabine Phosphate
Given IV

Drug: Mycophenolate Mofetil
Given IV or PO

Drug: Thiotepa
Given IV

Radiation: Total-Body Irradiation
Undergo high dose or middle intensity TBI

Procedure: Umbilical Cord Blood Transplantation
Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB transplantation




Primary Outcome Measures :
  1. Time to engraftment [ Time Frame: Up to 100 days post-transplant ]

Secondary Outcome Measures :
  1. Platelet engraftment (20k) [ Time Frame: Up to 2 years ]
  2. Incidence of infectious complications [ Time Frame: Up to 100 days post-transplant ]
  3. Overall survival [ Time Frame: Up to 2 years ]
  4. Non-relapse mortality [ Time Frame: Up to 2 years ]
  5. Incidence and severity of acute and chronic graft versus host disease [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   6 Months to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age criteria:

    • High dose TBI regimen: 6 months to =< 45 years
    • Middle intensity TBI regimen: 6 months to =< 65 years
    • Conditioning regimen selection should be based on the underlying disease, presence of minimal residual disease (MRD), age, co-morbidities, attending physician, and site preference; conditioning regimen will not require stratification of the randomization due to heterogeneity in the cohort of eligible patients.
  • Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia

    • All patients must have acute myeloid leukemia (AML) that is considered best treated by stem cell transplant by the referring physician and the attending transplant physician
    • All patients must be in complete remission (CR) as defined by < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age
    • 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 prior to enrollment
  • Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia

    • High risk first complete remission (CR1) (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia [MLL] rearrangements, hypodiploid); or high risk (HR) as defined by referring institution treatment protocol greater than 1 cycle to obtain CR; second complete remission (CR2) or greater
    • 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 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 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 tyrosine kinase inhibitor therapy
  • Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., 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% by a representative bone marrow aspirate morphology
  • Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1
  • Lansky (< 16 years old) >= 60
  • Adults: calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL
  • Children (< 18 years old): calculated creatinine clearance must be > 60 mL/min
  • Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
  • Transaminases must be < 3 x the upper limit of normal per reference values of referring institution
  • Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal
  • For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air
  • May not be on supplemental oxygen
  • Left ventricular ejection fraction > 45% OR
  • Shortening fraction > 26%
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • 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
  • Prior myeloablative transplant containing full dose TBI (greater than 8 Gy)
  • Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning; diagnostic lumbar puncture is to be performed per protocol
  • Patients >= 45 years: comorbidity score of 5 or higher

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01690520


Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States, 94304
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80217-3364
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Nohla Therapeutics, Inc.
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Filippo Milano Fred Hutch/University of Washington Cancer Consortium

Responsible Party: Nohla Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT01690520     History of Changes
Other Study ID Numbers: 2603.00
NCI-2012-01572 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2603
2603.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
P50HL110787 ( U.S. NIH Grant/Contract )
First Posted: September 21, 2012    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Biphenotypic, Acute
Leukemia, Lymphocytic, Chronic, B-Cell
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Cyclosporins
Cyclosporine
Thiotepa
Fludarabine