Allogeneic Stem Cell Transplantation of NiCord, Umbilical Cord Blood-derived Ex Vivo Expanded Stem and Progenitor Cells, in Adolescents and Adult Patients with Hematological Malignancies
- Conditions
- bone marrow cancerleukemia10024324
- Registration Number
- NL-OMON43606
- Lead Sponsor
- Gamida Cell ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
1.Patients must be 12-65 years of age
2.Patients with one of the following hematologic malignancies:
Acute lymphoblastic leukemia (ALL) at one of the following stages:
a.High risk first complete morphologic remission (CR1), defined as one or more of the following:
*The presence of t(4;11), t(9;22), t(1;19) or MLL rearrangements t(11q23)
*Extreme leukocytosis (WBC >30,000/µl for B-ALL or >100,000/µl for T-ALL)
*Longer than 4 weeks to achieve complete remission after induction therapy
b.Second or subsequent remission
*Acute myelogenous leukemia (AML) at one of the following stages:
a.First complete morphologic remission (CR1) that is NOT considered as favorable-risk:
Favorable risk is defined as having one of the following:
*t(8,21) without cKIT mutation
*inv(16) without cKIT mutation or t(16;16)
*Normal karyotype with mutated NPM1 and no FLT-3 Internal Tandem Duplication
*Normal karyotype with double mutated CEBPA
*APL in first or second molecular remission at end of consolidation
b.Second or subsequent remission
*Chronic myelogenous leukemia (CML) at one of the following phases:
a.Chronic phase with one or more of the following characteristics:
*Failure to achieve a primary hematologic or cytogenetic response to either nilotinib or dasatinib (following European LeukemiaNet timelines)
*Intolerance to/failure of two tyrosine kinase inhibitors (TKI)
*Any T3151 mutation
b.Accelerated phase with one or more of the following characteristics:
*Newly diagnosed patients who do not achieve an optimal response to TKIs
*TKI-treated patients who progress from chronic phase
c.Blast crisis (myeloid or lymphoid) with disease control
*Myelodysplastic Syndrome (MDS) with International history of International Prognostic Scoring System (IPSS) risk category of INT-1 or greater. On screening morphologic analysis patients must have no circulating myeloblasts and <10% myeloblasts in the bone marrow. MDS patients categorized as INT-1 on primary presentation must have life threatening neutropenia or thrombocytopenia.
*Lymphoma fulfilling one of the following criteria:
a.Chemotherapy-sensitive (complete or partial response) lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are INELIGIBLE for an autologous transplant.
b.Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan).
3.Patients must have a partially HLA-matched CBU: the unit must be HLA-matched at 4-6/6 HLA class I (HLA-A & HLA-B, low resolution) and II (HLA-DRB1, high resolution) loci with the patient. The CBU must have a pre-cryopreserved (post-processing), total CD34+ cell count of >=8 x10^6 as well as a pre-cryopreserved (post-processing) total nucleated cell count of >=1.8x10^9 and total nucleated cell dose >=1.8x10^7 TNC/kg. The CBU will have undergone volume reduction (both plasma and red blood cell depletion) prior to cryopreservation.
4.Patients must have an additional partially HLA-matched CBU, or two CBUs, reserved as a backup in case of batch failure. The backup CBU/s must be HLA-matched at 4-6/6 HLA class I (HLA-A & HLA-B, low resolution) and II (HLA-DRB1, high resolution) loci with the patient, and must have a pre-cryopreserved, total nucleated cell dose of at least 2x10^7 per kilogram, in case of one CBU, or 3x10^7 per kilogram, in ca
1. NK cell lymphoma, Burkitt's lymphoma
2. CLL/SLL diagnosis
3. MDS or CML with "marked" or "3+" fibrosis
4. CCMoL or MDS/CMMoL overlap
5. Less than 21 days have elapsed since initiation of the patient's last chemotherapy regimen and the initiation of the stem cell transplant preparative regimen (intrathecal agents, hydroxyurea, tyrosine kinase inhibitors, hypomethylating agents and rituximab, not considered chemotherapy)
6. Persistent clinically significant toxicities that, in the investigator's opinion, make the patient unsuitable for transplant
7. Evidence of anti-HLA antibodies to the selected NiCord® CBU (MFI>3000)
8. Evidence of HIV infection or HIV positive serology
9. Evidence of active Hepatitis B, Hepatitis C or EBV as determined by serology or PCR
10. Pregnancy (βHCG +) or lactation
11. Active malignancy other than that for which the UCB transplant is being performed within 12 months of enrollment. Fully resected cutaneous squamous cell or basal cell carcinoma or cervical carcinoma in situ within 12 months of enrollment will be permitted.
12. Evidence of uncontrolled bacterial, fungal or viral infections or severe concomitant diseases, which in the judgment of the Principal Investigator indicate that the patient could not tolerate transplantation
13. Patients with signs and symptoms of active central nervous system (CNS) disease, including CNS leukemia or lymphoma
14. Patients with an 8/8 allele level HLA-matched and readily available related or unrelated donor, e.g. patients who have haploidentical related donors will not be excluded
15. Prior allogeneic hematopoietic stem cell transplant
16. Allergy to bovine, gentamicin, or to any other product which may interfere with the treatment
17. Psychiatric illness and/or social situations that would limit compliance with study requirements
18. Enrolled in another clinical trial or received an investigational treatment during the last 30 days, unless documented approval obtained from Sponsor
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Incidence of NiCord®-derived neutrophil engraftment at 42 days following<br /><br>transplantation<br /><br>• Incidence of secondary graft failure at 180 days following transplantation of<br /><br>NiCord®</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Time from infusion to neutrophil engraftment<br /><br>• Time from infusion to platelet engraftment<br /><br>• Incidence of platelet engraftment at 100 days<br /><br>• Proportion of non-relapse mortality at 100 days<br /><br>• Incidence of acute GvHD grade II-IV and III-IV at 100 days<br /><br>• Incidence of chronic GvHD (limited or extensive) at 180 days and 1 year<br /><br>• Incidence of secondary graft failure at 1 year following transplantation of<br /><br>NiCord®<br /><br>• Overall survival at 180 days and 1 year<br /><br>• Safety and tolerability of NiCord® transplantation</p><br>