RECRUITING

Cord Blood Transplant in Children and Young Adults With Blood Cancers and Non-malignant Disorders

Conditions

AML ALL MDS MPD Withou Myelofibrosis NHL or HL Inherited Metabolic Disorders Hemoglobinopathies Bone Marrow Failure HLH Acute myelogenous leukemia Myelodysplasia Myeloproliferative Disorder Therapy-Related AML and MDS Therapy-Related Acute Myeloid Leukemia T-AML High-risk cytogenetics Cord Blood Transplantation 20-480 Memorial Sloan Kettering Cancer Center

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a single-arm study to investigate 1-year treatment related mortality (TRM) in patients with life threatening non-malignant and malignant hematologic disorders who do not have a matched related donor for allogeneic transplantation.

Official Title

Cord Blood Transplantation in Children and Young Adults With Hematologic Malignancies and Non-malignant Disorders

Quick Facts

Study Start:2020-11-20

Study Completion:2025-12-20

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04644016

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 21 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Complete first remission (CR1) at high risk for relapse such as any of the following: * Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder (MPS). * Therapy-related AML (t-AML). * White cell count at presentation \> 100,000. * Presence of extramedullary leukemia at diagnosis. * Any unfavorable subtype by FAB or WHO classification. * High-risk cytogenetics (e.g. those associated with MDS, abnormalities of 5, 7, 8, complex karyotype) or high-risk molecular abnormalities. * Requirement for 2 or more inductions to achieve CR1. * Presence of Minimal Residual Disease (MRD+) by cytogenetics, flow cytometry or molecular methods after induction. * Any patient with newly diagnosed AML with intermediate risk cytogenetics who elects allograft with curative intent over consolidation chemotherapy. * Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician. * Other high-risk features not defined above. * Complete second remission (CR2). * Primary refractory or relapsed AML with less than 10% blasts by bone marrow morphology. Patients with cytogenetic, flow cytometric, or molecular abnormalities in ≤ 10% of cells are eligible. * Complete first remission (CR1) at high risk for relapse such as any of the following: * White cell count at presentation \> 30,000 for B-cell lineage and \> 100,000 for T-cell lineage. * Presence of any high-risk cytogenetic abnormalities such as t (9;22), t (1;19), t (4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality. * Failure to achieve complete remission (CR) after four weeks of induction therapy. * Persistence or recurrence of MRD on therapy. * Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician. * Other high-risk features not defined above. * Complete second remission (CR2). * Primary refractory or relapsed ALL with MRD disease after antibody therapy (e.g., blinatumomab, inotuzumab, other) and/or CAR-T cell therapy. * International prognostic scoring system (IPSS) risk score of INT-2 or high risk at the time of diagnosis. * Any IPSS risk category if life-threatening cytopenia(s) exists. * Any IPSS risk category with karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia. * MDS/ myeloproliferative disorder overlap syndromes without myelofibrosis. * MDS/ MPD patients must have less than 10% bone marrow myeloblasts and ANC ≥ 0.2 (growth factor supported if necessary) at transplant work-up. * Eligible patients with aggressive histology (such as, but not limited to, diffuse large B-cell NHL, mantle cell NHL, and T-cell histology) in CR. * Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) will have 2nd or subsequent progression with stable disease/ CR/ PR with no single lesion equal to or more than 5 cm. * Eligible patients with HL will be those without progression of disease (POD) after salvage chemotherapy with no single lesion ≥ 5 cm. * Hurler Syndrome * Hunter (MPS 2 - early disease) * Sly syndrome (MPSVIII) * α-Mannosidosis * X- ALD * Osteopetrosis * Metachromatic Leukodystrophy * Globoid (GLD) * Hemoglobinopathies * Bone Marrow Failure syndromes * Immunodeficiencies, including HLH * Karnofsky or Lansky score ≥ 70% (see Appendix) * Bilirubin ≤ 1.5 mg/dL (unless benign congenital hyperbilirubinemia). * ALT ≤ 3 x upper limit of normal. * Pulmonary function (spirometry and corrected DLCO) ≥ 50% predicted (corrected for hemoglobin) . * Left ventricular ejection fraction ≥ 50%. * Age-adjusted Hematopoietic Cell Transplantation-Comorbidity Index (aaHCT-CI) less than or equal to 7. * Renal: serum creatinine ≤ 1.5x normal for age. If serum creatinine is outside the normal range, then CrCl \> 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) \>30% of predicted normal for age. * Each CB unit must be at least 3/8 HLA-matched to the patient considering high-resolution 8-allele HLA typing. * For malignant diseases follow MSKCC CBU selection algorithm * For non-malignant diseases, CBU will be required to have \> 5 x 107 TNC/kg; high HLA allele level match is preferable	* Inadequate performance status/ organ function. * Advanced metabolic disease (EBMT handbook). * Active CNS leukemic involvement. * Indolent NHL or Hodgkin lymphoma with progression of disease after most recent salvage chemotherapy. * Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis. * Autologous stem cell transplant within the preceding 6 months. * Any prior allogeneic stem cell transplant. * Active and uncontrolled infection (bacterial/fungal/viral) at time of transplantation. * HIV infection. * Seropositivity for HTLV-1. * Pregnancy or breast feeding. * Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, long-term follow-up, and research tests.

Inclusion Criteria

Exclusion Criteria

* Complete first remission (CR1) at high risk for relapse such as any of the following:
* Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder (MPS).
* Therapy-related AML (t-AML).
* White cell count at presentation \> 100,000.
* Presence of extramedullary leukemia at diagnosis.
* Any unfavorable subtype by FAB or WHO classification.
* High-risk cytogenetics (e.g. those associated with MDS, abnormalities of 5, 7, 8, complex karyotype) or high-risk molecular abnormalities.
* Requirement for 2 or more inductions to achieve CR1.
* Presence of Minimal Residual Disease (MRD+) by cytogenetics, flow cytometry or molecular methods after induction.
* Any patient with newly diagnosed AML with intermediate risk cytogenetics who elects allograft with curative intent over consolidation chemotherapy.
* Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician.
* Other high-risk features not defined above.
* Complete second remission (CR2).
* Primary refractory or relapsed AML with less than 10% blasts by bone marrow morphology. Patients with cytogenetic, flow cytometric, or molecular abnormalities in ≤ 10% of cells are eligible.
* Complete first remission (CR1) at high risk for relapse such as any of the following:
* White cell count at presentation \> 30,000 for B-cell lineage and \> 100,000 for T-cell lineage.
* Presence of any high-risk cytogenetic abnormalities such as t (9;22), t (1;19), t (4;11) or other MLL rearrangements (11q23) or other high-risk molecular abnormality.
* Failure to achieve complete remission (CR) after four weeks of induction therapy.
* Persistence or recurrence of MRD on therapy.
* Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.
* Other high-risk features not defined above.
* Complete second remission (CR2).
* Primary refractory or relapsed ALL with MRD disease after antibody therapy (e.g., blinatumomab, inotuzumab, other) and/or CAR-T cell therapy.
* International prognostic scoring system (IPSS) risk score of INT-2 or high risk at the time of diagnosis.
* Any IPSS risk category if life-threatening cytopenia(s) exists.
* Any IPSS risk category with karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia.
* MDS/ myeloproliferative disorder overlap syndromes without myelofibrosis.
* MDS/ MPD patients must have less than 10% bone marrow myeloblasts and ANC ≥ 0.2 (growth factor supported if necessary) at transplant work-up.
* Eligible patients with aggressive histology (such as, but not limited to, diffuse large B-cell NHL, mantle cell NHL, and T-cell histology) in CR.
* Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) will have 2nd or subsequent progression with stable disease/ CR/ PR with no single lesion equal to or more than 5 cm.
* Eligible patients with HL will be those without progression of disease (POD) after salvage chemotherapy with no single lesion ≥ 5 cm.
* Hurler Syndrome
* Hunter (MPS 2 - early disease)
* Sly syndrome (MPSVIII)
* α-Mannosidosis
* X- ALD
* Osteopetrosis
* Metachromatic Leukodystrophy
* Globoid (GLD)
* Hemoglobinopathies
* Bone Marrow Failure syndromes
* Immunodeficiencies, including HLH
* Karnofsky or Lansky score ≥ 70% (see Appendix)
* Bilirubin ≤ 1.5 mg/dL (unless benign congenital hyperbilirubinemia).
* ALT ≤ 3 x upper limit of normal.
* Pulmonary function (spirometry and corrected DLCO) ≥ 50% predicted (corrected for hemoglobin) .
* Left ventricular ejection fraction ≥ 50%.
* Age-adjusted Hematopoietic Cell Transplantation-Comorbidity Index (aaHCT-CI) less than or equal to 7.
* Renal: serum creatinine ≤ 1.5x normal for age. If serum creatinine is outside the normal range, then CrCl \> 50 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2) \>30% of predicted normal for age.
* Each CB unit must be at least 3/8 HLA-matched to the patient considering high-resolution 8-allele HLA typing.
* For malignant diseases follow MSKCC CBU selection algorithm
* For non-malignant diseases, CBU will be required to have \> 5 x 107 TNC/kg; high HLA allele level match is preferable

* Inadequate performance status/ organ function.
* Advanced metabolic disease (EBMT handbook).
* Active CNS leukemic involvement.
* Indolent NHL or Hodgkin lymphoma with progression of disease after most recent salvage chemotherapy.
* Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
* Autologous stem cell transplant within the preceding 6 months.
* Any prior allogeneic stem cell transplant.
* Active and uncontrolled infection (bacterial/fungal/viral) at time of transplantation.
* HIV infection.
* Seropositivity for HTLV-1.
* Pregnancy or breast feeding.
* Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, long-term follow-up, and research tests.

Contacts and Locations

Study Contact

Maria I Cancio, MD

CONTACT

212-639-2446

canciom@mskcc.org

Jaap Jan Boelens, MD, PhD

CONTACT

212-639-3643

boelensj@mskcc.org

Principal Investigator

Maria Cancio, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Maria Cancio, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-11-20

Study Completion Date2025-12-20

Study Record Updates

Study Start Date2020-11-20

Study Completion Date2025-12-20

Terms related to this study

Keywords Provided by Researchers

Acute myelogenous leukemia
AML
Myelodysplasia
MDS
Myeloproliferative Disorder
Therapy-Related AML and MDS
Therapy-Related Acute Myeloid Leukemia
T-AML
High-risk cytogenetics
Cord Blood Transplantation
20-480
Memorial Sloan Kettering Cancer Center

Additional Relevant MeSH Terms

AML
ALL
MDS
MPD Withou Myelofibrosis
NHL or HL
Inherited Metabolic Disorders
Hemoglobinopathies
Bone Marrow Failure
HLH