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
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01690520 |
Recruitment Status : Unknown
Verified March 2019 by Nohla Therapeutics, Inc..
Recruitment status was: Active, not recruiting
First Posted : September 21, 2012
Last Update Posted : April 1, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
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) |
Actual Enrollment : | 163 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 |
Actual Primary Completion Date : | September 18, 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:
|
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:
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:
|
- Time to neutrophil engraftment [ Time Frame: Up to 55 days post-transplant ]
- Time to platelet engraftment (20k) [ Time Frame: Up to 100 days post-transplant ]
- Overall survival [ Time Frame: Up to 2 years ]
- Non-relapse mortality [ Time Frame: Up to 2 years ]
- Incidence of severe acute graft versus host disease [ Time Frame: Up to 100 days post-transplant ]
- Incidence of chronic graft versus host disease [ Time Frame: Up to 2 years ]

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 |
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

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
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 |
Principal Investigator: | Filippo Milano | Fred Hutch/University of Washington Cancer Consortium |
Responsible Party: | Nohla Therapeutics, Inc. |
ClinicalTrials.gov Identifier: | NCT01690520 |
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: | April 1, 2019 |
Last Verified: | March 2019 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Biphenotypic, Acute Myelodysplastic Syndromes Syndrome 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 Cyclosporine Mycophenolic Acid Cyclophosphamide Thiotepa Fludarabine Fludarabine phosphate Cyclosporins Immunosuppressive Agents |