Cord Blood Transplant in Adults With Blood Cancers

Non-Hodgkin's Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05884333
• Other study ID #: 23-143
• Status: Recruiting
• Phase: Phase 2
• Start date: May 22, 2023
• Est. completion date: May 22, 2028

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Ioannis Politikos, MD
• Phone: 646-608-3773
• Email: ABMTTRIALS[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: May 22, 2028
• Est. primary completion date: May 22, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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 (FVC and FEV1) and corrected DLCO) > 60% predicted.

• Left ventricular ejection fraction (MOD-bp)> 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. [Taken from the Cord Blood Summary]

• 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). [Taken from the Cord Blood Summary]

• 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). [Taken from the Cord Blood Summary]

• A minimum of one unit will be reserved as a backup graft. [Taken from the Cord Blood Summary]

• 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. [Taken from the Cord Blood Summary]

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Chronic Myelogenous Leukemia (CML)
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes (MDS)
• Myeloproliferative Disorder
• Myeloproliferative Disorders
• Non-Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Consent only)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Suffolk-Commack (Consent only)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Consent only)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Consent only)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Consent only)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Consent only)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival (OS)		1 year post transplant
Secondary	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

External Links

•   Memorial Sloan Kettering Cancer Center