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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04644016
Recruitment Status : Recruiting
First Posted : November 25, 2020
Last Update Posted : April 29, 2021
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
AML ALL MDS MPD Withou Myelofibrosis NHL or HL Inherited Metabolic Disorders Hemoglobinopathies Bone Marrow Failure HLH Drug: Clofarabine Drug: Fludarabine Drug: Busulfan Drug: Cyclosporine-A Drug: Mycophenolate Mofetil Biological: Cord Blood Graft Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cord Blood Transplantation in Children and Young Adults With Hematologic Malignancies and Non-malignant Disorders
Actual Study Start Date : November 20, 2020
Estimated Primary Completion Date : December 20, 2023
Estimated Study Completion Date : December 20, 2023


Arm Intervention/treatment
Experimental: Participants with non-malignant and malignant hematologic disorders
Participants with life threatening non-malignant and malignant hematologic disorders who do not have a matched related donor for allogeneic transplantation.
Drug: Clofarabine
Clofarabine 30 mg/m2
Other Name: Clolar

Drug: Fludarabine
Fludarabine 10 mg/m2
Other Name: Fludara

Drug: Busulfan
Busulfan per PK
Other Name: Busulfex

Drug: Cyclosporine-A
GVHD prophylaxis will consist of cyclosporine-A (CSA) and mycophenolate mofetil (MMF) starting day -3.
Other Name: CSA

Drug: Mycophenolate Mofetil
GVHD prophylaxis will consist of cyclosporine-A (CSA) and mycophenolate mofetil (MMF) starting day -3.
Other Name: MMF

Biological: Cord Blood Graft
The CB graft will be infused on day 0 per standard practice
Other Name: CB graft




Primary Outcome Measures :
  1. Treatment related mortality at 1 year after myeloablative cord transplant [ Time Frame: 1 year ]
    The primary objective of this study is to assess treatment related mortality (TRM) at 1 year after myeloablative cord transplant.



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.


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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Participant Inclusion Criteria:

Age and Donor Status:

Patients with age ≤ 21 years at time of consent with no available and suitably matched related or unrelated donor in the required time period.

Diagnoses :

I. Acute myelogenous leukemia (AML) :

  • 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.

II. Acute lymphoblastic leukemia (ALL):

  • 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.

III. Other acute leukemias:

Leukemias of ambiguous lineage or of other types (e.g. blastic plasmacytoid dendritic cell neoplasm) with less than 5% blasts by BM morphology. Patients with persistent/relapsed disease with cytogenetic, flow cytometric or molecular aberrations in ≤ 5% of cells are eligible.

IV. Myelodysplastic Syndrome (MDS) / Myeloproliferative Disorders (MPD) other than myelofibrosis:

  • 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.

V. Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) at high-risk of relapse or progression if not in remission:

  • 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.

VI. Inherited Metabolic Disorders [also see EBMT Handbook for discussion on patient eligibility for allogeneic transplant; in general, patients are considered early in the disease course, before they develop neurologic symptoms (46)]:

  • Hurler Syndrome
  • Hunter (MPS 2 - early disease)
  • Sly syndrome (MPSVIII)
  • α-Mannosidosis
  • X- ALD
  • Osteopetrosis
  • Metachromatic Leukodystrophy
  • Globoid (GLD)

VII. Non-Malignant disorders (other) [also see EBMT Handbook for criteria for transplant (46)]

  • Hemoglobinopathies
  • Bone Marrow Failure syndromes
  • Immunodeficiencies, including HLH

Organ Function and Performance Status Criteria:

  • 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.

Normal GFR in Children and Young Adults (Age) : Mean GFR +- SD (mL/min/1.73 m2)

1 week: 40.6 + / - 14.8 2-8 weeks: 65.8 + / - 24.8 >8 weeks: 95.7 + / - 21.7 2-12 years: 133.0 + / - 27.0 13-21 years (males): 140.0 + / - 30.0 13-21 years (females: 126.0 + / - 22.0

GFR, glomerular filtration rate; SD, standard deviation greater than 2 years old: Normal GFR is 100 mL/ min. Infants: GFR must be corrected for body surf ace area.

For metabolic diseases: disease status to be evaluated according to EBMT Handbook [45].

Graft Criteria

CB units will be selected according to the current MSKCC unit selection algorithm. High resolution 8 allele HLA typing and recipient HLA antibody profile will be performed. Cord unit selection will occur based on HLA-match, total nucleated cell (TNC) and CD34+ cell dose adjusted per patient body weight. The cord bank of origin will also be considered. Donor specific HLA antibodies, if present, will also be taken into consideration and may influence the selection of the graft. CB graft will consist of one or two CB units (CBU) based on MSKCC selection algorithm.

  • 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

Participant Exclusion Criteria:

  • 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.

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): NCT04644016


Contacts
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Contact: Maria I Cancio, MD 212-639-2446 canciom@mskcc.org
Contact: Jaap Jan Boelens, MD, PhD 212-639-3643 boelensj@mskcc.org

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Maria Cancio, MD    212-639-2446      
Contact: E.         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Maria Cancio, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04644016    
Other Study ID Numbers: 20-480
First Posted: November 25, 2020    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
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:
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Hemoglobinopathies
Pancytopenia
Metabolic Diseases
Disease
Pathologic Processes
Hematologic Diseases
Genetic Diseases, Inborn
Cyclosporine
Mycophenolic Acid
Fludarabine
Busulfan
Clofarabine
Cyclosporins
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents