Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies

NCT01682226 | Completed Phase 2 Results

• 1 other identifier: 12-153
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out whether the addition of blood stem cells from a close family member, when added to umbilical cord blood will make the transplant safer.

Conditions

Leukemia; Myelodysplastic Syndrome; Lymphoma

Keywords

CYCLOPHOSPHAMIDE (CYTOXAN); CYCLOSPORINE; FLUDARABINE; G-CSF; MYCOPHENOLATE MOFETIL (MMF); Cord Blood Transplantation; CliniMACS; 12-153

Outcome Measures

Primary Outcomes (1)

• Percent of Engrafted Participants With Successful Neutrophil Recovery

  The primary endpoint is neutrophil recovery ie the speed \[median (range) days to recovery\] and success \[day 45 cumulative incidence percent\].

  Day 45

Secondary Outcomes (1)

• Overall Survival

  up to 6 years

Study Arms (2)

A: standard risk group

EXPERIMENTAL

This is a 2 arm phase 2 study to obtain an estimate of the speed of neutrophil recovery after myeloablative CBT with abrogation of prolonged cytopenia by infusion of haploidentical family member T-cell depleted PBSC in patients with high-risk or advanced hematologic malignancies.

Device: CliniMACS Fractionation system (Arm A); Biological: Haploidentical donor CD34+ cells

B: high risk group

EXPERIMENTAL

This is a 2 arm phase 2 study to obtain an estimate of the speed of neutrophil recovery after myeloablative CBT with abrogation of prolonged cytopenia by infusion of haploidentical family member T-cell depleted PBSC in patients with high-risk or advanced hematologic malignancies.

Device: CliniMACS Fractionation system (Arm B); Biological: Haploidentical donor CD34+ cells

Interventions

CliniMACS Fractionation system (Arm A) DEVICE

7 days before transplant Admit to hospital. Line insertion 6 days before transplant Fludarabine (chemotherapy) Cyclophosphamide (chemotherapy) 5 days before transplant Fludarabine Thiotepa 4 days before transplant Fludarabine Thiotepa 3 days before transplant Fludarabine Start CSA and MMF 2 days before transplant Fludarabine and TBI (radiation therapy) 1 day before transplant TBI (radiation therapy) Day of transplant Transplant day (infuse cord blood) Day after cord blood transplant Infuse family member stem cells 7 days after transplant Start G-CSF

A: standard risk group

CliniMACS Fractionation system (Arm B) DEVICE

8 days before transplant Admit to hospital. Line insertion 7 days before transplant Fludarabine 6 days before transplant Fludarabine Cyclophosphamide 5 days before transplant Fludarabine Cyclophosphamide 4 days before transplant Rest 3 days before transplant TBI x 3 Start CSA and MMF 2 days before transplant TBI x 3 1 day before transplant TBI x 3 Day of transplant TBI x 2 then infuse cord blood 1 day after the cord blood transplant Infuse family member stem cells 7 days after transplant Start G-CSF

B: high risk group

Haploidentical donor CD34+ cells BIOLOGICAL

CB grafts will consist of two CB units 4-6/6 HLA-matched to the patient to augment graft cell dose and additional T-cell depleted PBSC from a haplo-identical donor.

A: standard risk group; B: high risk group

Eligibility Criteria

• Age: 2 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Note: protocol eligible patients according to the criteria outlined below will then be divided according to age, diagnosis, performance status, organ function, prior transplantation, hematopoietic cell transplant comorbidity index (HCT-CI)23, and CB TNC dose into those who are at standard risk (Arm A) or high risk (Arm B) for early post-transplant death for the purposes of applying stopping rules and outcome analysis.
• Age:
• o 2 - 70 years. Diagnosis of severe aplastic anemia: eligibility to be discussed with PI and Service Chief. Such patients will be assessed in Arm B.
• Diagnosis of high risk hematological malignancy:
• Any acute leukemia in first complete remission (CR) considered at high risk for relapse, or second or third CR, or relapse/refractory less than 10% blasts in bone marrow, or aplasia post-therapy. This includes de novo acute leukemia or acute leukemia that is therapy related or arising from an antecedent hematologic disorder including myelodysplasia (MDS), chronic myeloid leukemia (CML) or other myeloproliferative disorder.
• Juvenile myelomonocytic leukemia (JMML) in CR, or relapse with less than 10% bone marrow blasts.
• CML with tyrosine kinase inhibitor failure in chronic or accelerated phase or evolved to acute leukemia.
• MDS or other myeloproliferative disorder with life-threatening cytopenia(s), and/or red blood cell or platelet transfusion dependence, or patients with aplasia, or patients with excess blasts less than 10% blasts in the bone marrow at work-up.
• Aggressive lymphoma: patients in CR1 with disease at high risk of relapse or CR2-3.
• Indolent lymphoma or chronic lymphocytic leukemia (CLL): any disease status provided any transformed component is in CR.
• Hodgkin's lymphoma that is primary refractory or relapsed not suitable for other therapy and in PR or CR or small volume stable disease.
• Performance status:
• Karnofsky score ≥ 70 or Lansky score ≥ 70.
• Organ function:
• Resting left ventricular ejection fraction (LVEF) ≥ 50%.

You may not qualify if:

• Active CNS leukemia.
• Any acute leukemia (including prior myelodysplasia or CML blast crisis) with morphologic relapse or persistent disease ≥ 10% blasts in the BM, or doubling of the blasts in the blood in the 2 weeks preceding admission, or need for hydroxyurea in the 2 weeks prior to admission, or uncontrolled extra-medullary disease.
• Two prior stem cell transplants of any kind.
• One prior autologous stem cell transplant within the preceding 12 months.
• One prior allogeneic stem cell transplant within the preceding 24 months.
• Prior radiation therapy with 400 cGy or more of TBI. If 200 cGy of prior TBI then only 400 CGy of TBI on this protocol is permitted.
• Uncontrolled viral, bacteria or fungal infection at time of study enrollment.
• Sero-positive or NAT positive for HIV.
• Females who are pregnant or breast feeding.
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests
• Cord Blood Grafts:
• Units will be selected based on the HLA-match to the patient and individual cell doses of the units according to current MSKCC unit selection criteria. HLA-testing will be done using molecular techniques. The standard cord blood graft for this protocol will consist of 2 units as a double unit graft although single units are permitted. Each unit will be at least 4 of 6 HLA-A, -B antigen and -DRB1 allele matched with the recipient. Each unit of a double unit graft will have a cryopreserved dose of at least 1.5 x 10\^7 TNC/recipient body weight (TNC/kg). In the occasional patient with a large well matched good quality single unit or the rare patient with only one unit of suitable match and dose characteristics the cord blood graft can consist of a single unit as described in section 6.1 .
• A HLA-haploidentical related donor will be selected as available as per standard MSKCC Adult BMT guidelines. Mismatched family members who are matched at more than 5 of 10 HLA-loci are permitted. Factors to be taken into account when selecting a haplo-identical donor will include donor age, weight, health status and comorbidities, compliance, venous access, recipent donor specific HLA-antibody status, and NK cell alloreactivity.
• The donor must meet criteria outlined in the FACT-approved SOP for "DONOR EVALUATION AND SELECTION FOR ALLOGENEIC TRANSPLANTATION" in the Blood and Marrow Transplant Program Manual, document E-1 (see attached, or link to URL:(https://one.mskcc.org/sites/pub/corp/bmt/Documents/D2\_SOP\_Donor%20Selection%20and%20Evaluation\_04\_2015.pdf)
• The donor must have adequate peripheral venous catheter access for leukapheresis or must agree to placement of a central catheter.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Juliet Barker, MBBS
• Organization: Memorial Sloan Kettering Cancer Center

barkerj@mskcc.org

646-608-3756

Study Officials

• Juliet Barker, M.B.B.S.

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 10, 2012
• Study Start: September 5, 2012
• Primary Completion: January 8, 2021
• Study Completion: January 8, 2021
• Last Updated: August 5, 2022
• Results First Posted: August 5, 2022

Record last verified: 2021-01

Locations

US (1)