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

NCT01690520 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: 2603.00NCI-2012-015722603P30CA015704P50HL110787
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 8

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.

Conditions

Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Time to Neutrophil Engraftment

  First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.

  Up to 55 days post-transplant

Secondary Outcomes (5)

• Time to Platelet Engraftment (20k)

  Up to 100 days post-transplant

• Overall Survival

  Up to 2 years

• Non-relapse Mortality

  Up to 2 years

• Proportion of Patients With Severe Acute Graft Versus Host Disease

  Up to 100 days post-transplant

• Proportion of Participants With Chronic Graft Versus Host Disease

  Up to 2 years

Study Arms (2)

Arm I (standard of care)

ACTIVE COMPARATOR

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; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Drug: Mycophenolate Mofetil; Drug: Thiotepa; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Arm II (experimental)

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; 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

Interventions

Cyclophosphamide DRUG

Given IV

Arm I (standard of care); Arm II (experimental)

Cyclosporine DRUG

Given IV or PO

Arm I (standard of care); Arm II (experimental)

Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion BIOLOGICAL

Given IV

Also known as: NLA101, Dilanubicel

Arm II (experimental)

Fludarabine Phosphate DRUG

Given IV

Arm I (standard of care); Arm II (experimental)

Mycophenolate Mofetil DRUG

Given IV or PO

Arm I (standard of care); Arm II (experimental)

Thiotepa DRUG

Given IV

Arm I (standard of care); Arm II (experimental)

Total-Body Irradiation RADIATION

Undergo high dose or middle intensity TBI

Arm I (standard of care); Arm II (experimental)

Umbilical Cord Blood Transplantation PROCEDURE

Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant

Also known as: Cord Blood Transplantation, UCB transplantation

Arm I (standard of care); Arm II (experimental)

Eligibility Criteria

• Age: 6 Months - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nohla Therapeutics, Inc.: lead
• National Cancer Institute (NCI): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (8)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

Location

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; Cyclosporine; fludarabine phosphate; Mycophenolic Acid; Thiotepa; Whole-Body Irradiation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Deverra Therapeutics

cdelaney@deverratx.com

206-519-5304

Study Officials

• Filippo Milano

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2012
• First Posted: September 21, 2012
• Study Start: December 11, 2012
• Primary Completion: September 18, 2018
• Study Completion: May 29, 2020
• Last Updated: July 6, 2021
• Results First Posted: July 6, 2021

Record last verified: 2021-06

Locations

US (8)