Targeting the IPA and Matching for the Non-Inherited Maternal Antigen for Haplo-Cord Transplantation

NCT01810588 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 1205012383
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 2

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.

Conditions

Hematologic Malignancies

Keywords

Allogeneic transplant; Hematologic Malignancies; Acute Leukemia; Myeloproliferative disorders; Lymphoma; Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Who Achieved Engraftment With De-Escalating Umbilical Cord Total Nucleated Cell (TNC) Dose

  We aim to identify the lowest threshold of umbilical cord total nucleated cell (TNC) dose that can be utilized assure durable umbilical cord blood engraftment in the haplo-cord transplants. The threshold will be defined as the lowest dose which assures cord blood engraftment occurs in at least 80% of subjects.

  100 days

Secondary Outcomes (3)

• Long-term Survival of Subjects Undergoing Haplo-cord Transplants

  5 years after transplant

• Impact of IPA Targeting on Transplant Outcome

  5 years from transplantation

• Impact of NIMA Matching on Transplant Outcome

  5 years from transplantation

Study Arms (4)

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg

EXPERIMENTAL

All subjects in this cohort will receive a minimal cell dose of 2 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell 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. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, 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.

Device: CliniMACS® CD34 Reagent System; Drug: Fludarabine; Drug: Melphalan; Drug: anti-thymocyte globulin (rabbit); Drug: Rituximab; Radiation: Total Body Irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg

EXPERIMENTAL

All subjects in this cohort will receive a minimal cell dose of 1 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell 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. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, 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.

Device: CliniMACS® CD34 Reagent System; Drug: Fludarabine; Drug: Melphalan; Drug: anti-thymocyte globulin (rabbit); Drug: Rituximab; Radiation: Total Body Irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg

EXPERIMENTAL

All subjects in this cohort will receive a minimal cell dose of 0.5 x 10\^7 total nucleated cells (TNC)/kilogram (kg) for the umbilical cord blood unit. Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell 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. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, 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.

Device: CliniMACS® CD34 Reagent System; Drug: Fludarabine; Drug: Melphalan; Drug: anti-thymocyte globulin (rabbit); Drug: Rituximab; Radiation: Total Body Irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Cohort 4

EXPERIMENTAL

All subjects in this cohort will receive the minimum required cell dose that is determined following the dose de-escalation portion of the study (cohorts 1 through 3) Haplo-cord transplantation: All subjects will receive a conditioning regimen of chemotherapy prior to stem cell 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. For the transplant component of treatment, subject will receive umbilical cord blood. The study involves transplantation of unlicensed units of cord blood. Therefore, these are considered investigational products. In addition to the umbilical cord blood unit, 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.

Device: CliniMACS® CD34 Reagent System; Drug: Fludarabine; Drug: Melphalan; Drug: anti-thymocyte globulin (rabbit); Drug: Rituximab; Radiation: Total Body Irradiation; Drug: Mycophenolate Mofetil; Drug: Tacrolimus

Interventions

CliniMACS® CD34 Reagent System DEVICE

The stem cells from the haplo-identical donor will be purified by a procedure called CD34 selection before they are given to the subject. A special device called the CliniMACS® CD34 Reagent System, which is not FDA approved, will be used for this purpose. The manufacturer of the device, Miltenyi Biotec, is providing the researchers access to the device for use in this research study. Because the stem cells from the haplo-identical donor are treated using the CliniMACS CD34 selection device, they cells are considered investigational.

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Fludarabine DRUG

Administer 30 mg/m2 /day intravenously x 5 days (Day -7 to Day -3) of a total dose of 150 mg/m2. Fludarabine will be dosed according to actual body weight.

Also known as: Fludara, Fludarabine phosphate

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Melphalan DRUG

Administer 70mg/m2/day intravenously x 2 days. Melphalan will be dosed according to actual body weight. Cryotherapy with ice chips will be administered to prevent mucositis

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

anti-thymocyte globulin (rabbit) DRUG

Administer 1.5 mg/kg/day intravenously x 3 days, total 4.5 mg/kg. ATG will be dosed according to actual body weight. The first dose will be infused over at least six hours, and subsequent doses over at least 4 hours. Pre-medications include acetaminophen 650 mg by mouth, diphenhydramine 25-50 mg by mouth or intravenously, and methylprednisolone 2 mg/kg (1 mg/ kg at the initiation and 1 mg/kg half-way through anti-thymocyte globulin administration).

Also known as: rATG, Rabbit ATG

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Rituximab DRUG

Administer one dose of 375 mg/m2 prior to or upon admission for all patients not previously exposed to rituximab or who have not received rituximab in the six months prior to transplant.

Also known as: Rituxan

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Total Body Irradiation RADIATION

Patients at high risk of CNS relapse (e.g. ALL or Burkitt's lymphoma) or patients at high risk for graft rejection (i.e., donor-specific HLA antibodies, patients with severe aplastic anemia, or hemoglobinopathies) may receive 2 doses of TBI as part of the conditioning.

Also known as: TBI

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Mycophenolate Mofetil DRUG

Will be started on Day -2 and given at a dose of 1000 mg every 8 hours until Day 28. Mycophenolae Mofetil can be given orally or intravenously. Infection, toxicity, very low patient weight (\<50 kilograms) may prompt earlier discontinuation or adjustment of doses.

Also known as: Cellcept, MMF

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Tacrolimus DRUG

Administered 0.03/mg/kg/day intravenous continious infusion (CI) over 24 hours from 4pm Day -2 until engraftment or when subject is able to take orally, then tacrolimus approximately 0.09 mg/kg orally in 2 divided doses. Tacrolimus should be given at full dose to maintain levels of 5-15 ng/mL through Day 180, tapered by 20% every week thereafter. Infection, toxicity or other clinical circumstances may prompt earlier discontinuation or adjustment of doses. In the presence of Graft versus Host Disease, a clinical decision by the attending physician will determine if tacrolimus can be tapered or should be continued. Oral tacrolimus can be used when intravenous access for CI tacrolimus is unavailable.

Also known as: Prograf

Cohort 1 - Minimum Cell Dose 2 x 10^7 TNC/kg; Cohort 2 - Minimum Cell Dose 1 x 10^7 TNC/kg; Cohort 3 - Minimum Cell Dose 0.5 x 10^7 TNC/kg; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must have a confirmed diagnosis of:
• Previously Relapsed or refractory acute leukemia (myeloid or lymphoid)
• Acute leukemia in first remission at high-risk for recurrence
• Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis
• Recurrent or refractory malignant lymphoma or Hodgkin lymphoma
• Chronic lymphocytic leukemia, relapsed or with poor prognostic features
• Multiple myeloma
• Myelodysplastic syndrome
• Chronic myeloproliferative disease
• Hemoglobinopathies
• Aplastic anemia
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (2)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Related Publications (2)

• 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.

  PMID: 31217161 DERIVED

• 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.

  PMID: 26869630 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Myeloproliferative Disorders; Lymphoma; Neoplasms, Plasma Cell

Interventions

fludarabine; fludarabine phosphate; Melphalan; Antilymphocyte Serum; thymoglobulin; Rituximab; Whole-Body Irradiation; Mycophenolic Acid; Tacrolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Radiotherapy; Therapeutics; Investigative Techniques; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Results Point of Contact

• Title: Alexandra Gomez Arteaga, MD
• Organization: Weill Cornell Medicine

alg9117@med.cornell.edu

646-962-7950

Study Officials

• Alexandra Gomez Arteaga, MD

  Weill Medical College of Cornell University

  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: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: March 13, 2013
• Study Start: October 16, 2012
• Primary Completion: August 9, 2023
• Study Completion (Estimated): April 1, 2028
• Last Updated: September 2, 2025
• Results First Posted: October 9, 2024

Record last verified: 2025-08

Locations

US (2)