Cord Blood Transplant in Adults With Blood Cancers

Optimized Cord Blood Transplantation for the Treatment of High-Risk Hematologic Malignancies in Adults

Cord blood transplants (CBT) are a standard treatment for adults with blood cancers. MSK has developed a standard ("optimized") practice for cord blood transplant (CBT). This optimized practice includes how patients are evaluated for transplant, the conditioning treatment (standard chemotherapy and total body irradiation therapy) given to prepare the body for transplant, the amount of stem cells transplanted, and how patients are followed during and after transplant.The purpose of this study is to collect information about participant outcomes after CBT following MSK's optimized practice. The researchers will look at outcomes of the CBT treatment such as side effects, disease relapse, GVHD, and immune system recovery after CBT treatment.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin's Lymphoma; Myelodysplastic Syndromes (MDS); Acute Lymphoblastic Leukemia (ALL); Myeloproliferative Disorder; Acute Myelogenous Leukemia (AML); Chronic Myelogenous Leukemia (CML)
• Intervention / Treatment: Drug: Conditioning Chemotherapy; Biological: Cord blood graft

• Study Type: Interventional
• Enrollment (Estimated): 54
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ioannis Politikos, MD; Phone Number: 646-608-3773; Email: ABMTTrials@mskcc.org
• Study Contact Backup: Name: Juliet Barker, MBBS; Phone Number: 646-608-3756

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Consent only)
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Consent only)
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Consent only)
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk-Commack (Consent only)
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Consent only)
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773; Email: ABMTTrials@mskcc.org
      • Contact: Juliet Barker, MBBS; Phone Number: 646-608-3756
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Consent only)
      • Contact: Ioannis Politikos, MD; Phone Number: 646-608-3773

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 (MPD).
  • Therapy-related AML.
  • Presence of extramedullary leukemia at diagnosis.
  • Requirement for 2 or more inductions to achieve CR1.
  • Intermediate or high ELN2017 genetic risk AML.
  • 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) or greater (CR2+).
• Patients in morphologic remission with persistent cytogenetic, flow cytometric, or molecular aberrations are eligible

II. Acute lymphoblastic leukemia (ALL):

• Complete first remission (CR1) at high risk for relapse such as any of the following:

  • 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 MRD- complete remission after induction therapy.
  • Persistence or recurrence of minimal residual disease 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) or greater (CR2+). Note: ALL with less than 5% blasts at time of transplant but persistent cytogenetic, flow cytometric or molecular aberrations are eligible.

III. Other acute leukemias: Acute leukemias of ambiguous lineage or mixed phenotype with less than 5% blasts. Leukemias in morphologic remission with persistent cytogenetic, flow cytometric or molecular aberrations are eligible.

IV. Myelodysplastic Syndromes (MDS) and 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/MPD 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) at high-risk of relapse or progression if not in remission:

Eligible patients with aggressive histologies (such as, but not limited to, diffuse large B-cell NHL, mantle cell NHL, and T-cell histologies) in CR by PET/CT imaging.

o Eligible patients with indolent B-cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) will have 2 nd or subsequent progression with PR or CR by PET/CT imaging.

VI. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) in morphologic remission.

Prior treatment:

To prevent graft rejection, patients who received only non-lymphodepleting agents for their malignancy (hypomethylating agents, venetoclax, hydroxyurea, TKIs etc.), or patients who received lymphodepleting chemotherapy > 3 months prior to scheduled admission, should receive fludarabine 25 mg/m2 daily x 3 days for lymphodepletion 14-42 days (aiming for 2-4 weeks) prior to admission in order to qualify for the protocol.

Organ Function and Performance Status Criteria:

• Karnofsky score equal or greater than 80% (See Appendix B; inpatient Leukemia service transfers without discharge are acceptable provided patient has equivalent KPS as if were outpatient).
• Calculated creatinine clearance > 70 ml/min.
• Bilirubin < 1.5 mg/dL (unless benign congenital hyperbilirubinemia or hemolysis).
• ALT < 3 x upper limit of normal (ULN).
• Pulmonary function (spirometry and corrected DLCO) > 60% predicted.
• Left ventricular ejection fraction > 50%.
• Albumin > 3.0.
• Hematopoietic Cell Transplantation Comorbidity index (HCT-CI) ≤5.

Graft criteria:

Two CB units will be selected according to current MSKCC CB unit selection algorithm. High resolution 8-allele HLA typing and recipient HLA antibody profile will be performed. Unit selection will occur based on HLA-match, total nucleated cell (TNC) and CD34+ cell dose adjusted per patient body weight. The 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.

• Each CB unit must be at least 3/8 HLA-matched to the patient considering high-resolution 8-allele HLA typing.
• Each CB unit will be required to have a cryopreserved TNC dose of at least 1.5 x 10^7 TNC/ recipient body weight (TNC/ kg).
• Each CB unit will be required to have a cryopreserved CD34+ cell dose of at least 1.5 x 10^5 CD34+ cells/ recipient body weight (CD34+ cells/kg).
• A minimum of one unit will be reserved as a backup graft.
• Each CB unit will be required to be cryopreserved in standard cryovolume (24-27 ml/s per unit or per bag if unit in two bags) and be red blood cell depleted.

Exclusion Criteria:

• Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis.
• Patients persistent with CNS involvement in CSF or CNS imaging at time of screening
• Prior checkpoint inhibitors/ blockade in the last 12 months.
• Two prior stem cell transplants of any kind.
• One prior autologous stem cell transplant within the preceding 12 months.
• Prior allogeneic transplantation.
• Prior involved field radiation therapy that would preclude safe delivery of 400cGy TBI in the opinion of Radiation Oncology.
• Active and uncontrolled infection at time of transplantation.
• HIV infection.
• Seropositivity for HTLV-1.
• Inadequate performance status/ organ function.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cord Blood Transplant; Adult patients with high-risk hematologic malignancies and a suitable double-unit CB graft will undergo work-up to assess protocol eligibility. CB graft selection will be based on established MSKCC guidelines. Patients will receive standard conditioning with Cy 50 mg/kg, Flu 150 mg/m2, Thio 10 mg/kg, and TBI 400 cGy according to the eligibility criteria. GVHD prophylaxis will consist of CSA and MMF starting day -3. The double-unit CB graft will be infused on day 0 per standard practice. Optimized CBT practices, will be implemented in this protocol.

Drug: Conditioning Chemotherapy; Conditioning: Cyclophosphamide (CY) 50 mg/kg x1 (day -6), Fludarabine (FLU) 30 mg/m2 x5 (days -6 to -2), Thiotepa (THIO) 5 mg/kg x2 (days -5 & -4), Total Body Irradiation (TBI) 200 cGy x2 (days -2 & -1). GVHD prophylaxis: Cyclosporine (CSA) 3 mg/kg q12 hours & Mycophenolate Mofetil (MMF) 15 mg/kg q8 hours (starting IV day -3).; Biological: Cord blood graft; The double-unit CB graft will be infused on day 0 per standard practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	1 year post transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to neutrophil engraftment	The day of neutrophil recovery is the 1st day of 3 consecutive days of absolute neutrophil count (ANC) at or above 500 after the first post-CBT nadir.	Up to day 45 post-transplant

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Ioannis Politikos, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Estimated): May 22, 2028
• Study Completion (Estimated): May 22, 2028

Study Registration Dates

• First Submitted: May 22, 2023
• First Submitted That Met QC Criteria: May 22, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: FLUDARABINE; CYCLOPHOSPHAMIDE (CYTOXAN); CYCLOSPORINE A; MYCOPHENOLATE MOFETIL (MMF); Cord Blood Transplant; THIOTEPA; 23-143
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Leukemia, Lymphoid; Chronic Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders
• Other Study ID Numbers: 23-143

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No