Clinical trial NCT01810588: Targeting the IPA and Matching for the Non-Inherited Maternal Antigen for Haplo-Cord Transplantation
Official title: A Prospective Study of Optimal Cord Selection for Haplo-Cord Transplantation: Targeting the Inherited Paternal Antigen (IPA) and Matching for the Non-Inherited Maternal Antigen (NIMA)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hematologic Malignancies
Keywords: Allogeneic transplant
Hematologic Malignancies
Acute Leukemia
Myeloproliferative disorders
Lymphoma
Myeloma
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2013-03-13
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this trial, we aim to improve the outcomes of haplo cord transplant. Haplo cord transplant is a novel and promising way to improve transplant outcomes. We hypothesize that identification of a graft that is at least 5/6 matched and inherited paternal antigen (IPA) targeted (i.e., cord blood grafts share one or more IPA antigens with the prospective recipient) is more important to the outcome of haplo cord transplant than the nucleated cell dose. The identification of such a graft for a large proportion of the subjects may necessitate accepting a lower umbilical cord graft dose.

In addition to a umbilical cord blood transplant, recipients will receive stem cells from a family member ( a haplo-identical donor) . After collection and prior to infusion, these cells will be purified using a device called a CliniMACS CD34 selection device. The subject will undergo a chemotherapy conditioning regimen prior to transplantation. No experimental drugs are used in this study, and the combinations of drugs that will be used in the conditioning regimen are combinations that have been used in the past.

Detailed description: This is a clinical trial for subjects with hematologic malignancies ( acute leukemia, myeloproliferative disorders, lymphoma, myeloma) who are in need of a donor stem cell transplant, and for whom an umbilical cord blood transplant is thought to be the best option. As donors for allogeneic transplant, we typically try to use related family members, such as brothers or sisters, or volunteer donors who are 'HLA matched', i.e. share similar proteins on their cells. This study is for subjects for whom such a matched sibling donor or a matched unrelated donor is not available.

For such subjects a commonly used transplant procedure is to use stem cells from one or two umbilical cords (UCB) from a newborn. These umbilical cord blood grafts, despite not completely matching the recipient, cause few problems with graft vs host disease (a common complication of transplant). But they tend to grow very slowly and subjects often have very prolonged hospital stays and are at high risk for complications due to low blood counts. Umbilical cord blood transplant will be the standard arm for this protocol.

This study uses a new method of bone marrow transplantation called combined haplo-identical cord (haplo-cord) transplantation. In this procedure, cells from a related donor who shares half of the HLA proteins ( haplo-identical) are collected from the blood, as well as cells from an umbilical cord, and then both are transplanted. It is hoped that by using cells from a haplo-identical relative, subjects will have a faster recovery and require fewer transfusions. Over time the haplo-identical cells from the relative are replaced by the cells from the cord blood. The combined transplantation of haplo-identical stem cells and cord blood has previously been used in approximately 60 subjects with very encouraging results.

Traditionally it has been felt that the most important determinant of outcome of an UCB stem cell transplant is the cord blood cell dose. The second determinant is the degree of matching between donor and recipient. Many times, we have difficulty identifying UCB units of sufficient cell dose that are well matched. Of interest,in our prior study of haplo-cord SCT indicated outcomes seemed independent of the UCB cell dose. If this preliminary observation is correct, we may be able to improve the outcomes of haplo cord transplant further by accepting lower threshold UCB doses and rather focusing on optimal matching (including matching for HLA and another characteristic called IPA). This is the primary objective of this study.

Eligibility criteria: Inclusion Criteria:

* Subject must have a confirmed diagnosis of:

  1. Previously Relapsed or refractory acute leukemia (myeloid or lymphoid)
  2. Acute leukemia in first remission at high-risk for recurrence
  3. Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis
  4. Recurrent or refractory malignant lymphoma or Hodgkin lymphoma
  5. Chronic lymphocytic leukemia, relapsed or with poor prognostic features
  6. Multiple myeloma
  7. Myelodysplastic syndrome
  8. Chronic myeloproliferative disease
  9. Hemoglobinopathies
  10. Aplastic anemia
  11. Other hematological disorder in need of allogeneic transplant (e.g. blastoid dendritic cell neoplasm)
* Age ≥ 18 years
* Likely to benefit from allogeneic transplant in the opinion of the transplant physician
* An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.
* Karnofsky (KPS) Performance status of \>= 70%
* Acceptable organ function as defined below: Serum bilirubin: \< 2.0mg/dL ALT(SGPT): \< 3 X upper limit of normal Creatinine Clearance: \> 50 mL/min/1.73m2 (as estimated by the modified MDRD equation)
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Life expectancy is severely limited by concomitant illness or uncontrolled infection
* Severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired pulmonary function tests (PFT's)
* Evidence of chronic active hepatitis or cirrhosis
* Uncontrolled HIV disease
* Pregnant or lactating

Primary outcomes:
measure: Number of Subjects Who Achieved Engraftment With De-Escalating Umbilical Cord Total Nucleated Cell (TNC) Dose
timeFrame: 100 days
Secondary outcomes:
measure: Long-term Survival of Subjects Undergoing Haplo-cord Transplants
timeFrame: 5 years after transplant
measure: Impact of IPA Targeting on Transplant Outcome
timeFrame: 5 years from transplantation
measure: Impact of NIMA Matching on Transplant Outcome
timeFrame: 5 years from transplantation
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Alexandra Gomez Arteaga, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Besien K, Artz A, Champlin RE, Guarneri D, Bishop MR, Chen J, Gergis U, Shore T, Liu H, Rondon G, Mayer SA, Srour SA, Stock W, Ciurea SO. Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning. Blood Adv. 2019 Jun 25;3(12):1858-1867. doi: 10.1182/bloodadvances.2019000200.
citation: van Besien K, Hari P, Zhang MJ, Liu HT, Stock W, Godley L, Odenike O, Larson R, Bishop M, Wickrema A, Gergis U, Mayer S, Shore T, Tsai S, Rhodes J, Cushing MM, Korman S, Artz A. Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival. Haematologica. 2016 May;101(5):634-43. doi: 10.3324/haematol.2015.138594. Epub 2016 Feb 11.