Randomized HaploCord Blood Transplantation vs. Double Umbilical Cord Blood Transplantation for Hematologic Malignancies

NCT01745913 | Terminated Phase 2 Results DMC

• 1 other identifier: 1205012374
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is compare the efficacy of haplo-cord transplant (investigational arm) with that of a more commonly used procedure in which only the cells contained in one or two umbilical cords are infused (standard arm). We hypothesize that reduced intensity conditioning and haplo-cord transplant results in fast engraftment of neutrophils and platelets, low incidences of acute and chronic graft versus host disease, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay and promising long term outcomes. We also hypothesize that umbilical cord blood selection can prioritize matching and better matched donors can be identified rapidly for most subjects.

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma

Keywords

Leukemia; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of Neutrophil Engraftment After Combined Haplo-identical Cord With That of Umbilical Cord Blood Transplantation.

  No patients completed this study and are therefore inevaluable. Subject data not evaluable for the outcome measure time frame. Subject data only evaluable up to month 3.

  estimation of 24 months to determine engraftment rates for all subjects

Secondary Outcomes (5)

• Platelet Recovery After Transplant Regimens

  estimation of 24 months to determine platelet recovery for all subjects

• Transfusion Requirements After Haplo-identical Umbilical Cord Blood Transplant Versus Double Umbilical Cord Blood Transplant

  estimation of 24 months to determine transfusion requirements of all subjects

• Transplant-related Mortality (TRM), Relapse Rate, Survival and Progression Free Survival

  estimation of 24 months to obtain survival info between subjects

• Incidence of Acute and Chronic GVHD

  estimation of 24 months to obtain GVHD data on all subjects

• Severity of Opportunistic Infections

  estimation of 24 months to obtain infection data on all subjects

Study Arms (2)

Haplo-Cord SCT

EXPERIMENTAL

The UCB unit must supply a minimum of 1.0 x107/kg pre-cryopreserved nucleated cell dose. The unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1

Device: CliniMACS® CD34 Reagent System; Drug: Fludarabine; Drug: Melphalan; Drug: Rabbit ATG; Procedure: Haplo-Identical Cord Transplantation

UCB SCT

ACTIVE COMPARATOR

For the standard arm, UCB units will be selected using the Minnesota strategy and the strategy followed in a recent CTN study.17;19Each unit must supply a minimum of 1.5 x107/kg pre-cryopreserved nucleated cell dose. Subjects must have two partially HLA-matched UCB units. Each unit must match at a minimum of 4 of 6 at HLA-A, -B, -DRB1 loci with the recipient. This may include 0-2 antigen mismatches at each A or B (at the antigen level) or DRB1 (at the allele level) loci. All typing will be done using molecular typing. Though molecular level typing will be available, a match is defined at intermediate resolution for HLA-A and -B and at high resolution for -DRB1

Drug: Fludarabine; Drug: Melphalan; Drug: Rabbit ATG; Procedure: Double Umbilical Cord Blood Transplantation

Interventions

CliniMACS® CD34 Reagent System DEVICE

If a subject is randomized to the haplo-cord transplant group, their family member will undergo a stem cell collection. 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.

Also known as: Miltenyi CliniMACS® device

Haplo-Cord SCT

Fludarabine DRUG

Fludarabine: 30 mg/m2 /day intravenously x 5 days total dose 150 mg/m2. Fludarabine will be dosed according to actual body weight

Haplo-Cord SCT; UCB SCT

Melphalan DRUG

Melphalan: 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.

Haplo-Cord SCT; UCB SCT

Rabbit ATG DRUG

Rabbit ATG (rATG): 1.5 mg/kg/day intravenously x 4 days, total 6 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

Haplo-Cord SCT; UCB SCT

Double Umbilical Cord Blood Transplantation PROCEDURE

All subjects will receive an UCB dose of \> 3 x107/kg nucleated blood cells. It is expected that this will require co-infusion of two UCB in the large majority of cases. If two UCB are required, they will be at least 4/5 matched to the recipient.

Also known as: UCB SCT

UCB SCT

Haplo-Identical Cord Transplantation PROCEDURE

If randomized to the haplo-cord group, a family member will undergo a stem cell collection. In both arms, subjects will receive a "conditioning regimen" prior to transplantation. The conditioning regimen utilized in this study incorporates fludarabine-Melphalan and antithymocyte globulin (ATG). This regimen has the advantage of being nearly identical to the regimen utilized for our haplo-cord regimen is based on the experience of the Dana-Farber/Mass-General regimen.

Also known as: Haplo-cord transplant

Haplo-Cord SCT

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 histologically or cytologically confirmed diagnosis of: Acute Myelogenous Leukemia Myelodysplastic Syndrome Acute Lymphocytic Leukemia Lymphoma (Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma)
• Must be \> 18 years of age
• Subject is likely to benefit from allogeneic transplant in the opinion of the transplant physician
• An human leukocyte antigen (HLA)-identical related or unrelated donor cannot be identified within an appropriate time frame
• Karnofsky Performance Status (KPS) of \> 80
• Subject has acceptable organ and marrow function as defined below: Serum bilirubin \< 2.0mg/dL ALT(SGPT) 3 X upper limit of normal Creatinine Clearance \> 50 mL/min as estimated by the modified MDRD equation.18
• Ability to understand and the willingness to sign a written informed consent document.
• A preliminary search has identified both:
• Appropriate umbilical cords for a single, or if necessary a double umbilical cord blood (UCB) transplant AND
• An appropriate single UCB as well as an appropriate haplo donor for haplo-cord transplant

You may not qualify if:

• Myeloproliferative disorders, hemoglobinopathies, severe aplastic anemia or any diagnosis not listed under 3.1.1
• Life expectancy is severely limited by concomitant illness or uncontrolled infection
• Subjects with severely decreased Left Ventricular Ejection Fraction (LVEF) or impaired pulmonary function tests (PFTs)
• Subject has evidence of chronic active hepatitis or cirrhosis
• Subject is HIV-positive
• Subject is pregnant or lactating. -

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10026, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia; Lymphoma

Interventions

fludarabine; Melphalan; thymoglobulin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; 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

Results Point of Contact

• Title: Koen van Besien, MD
• Organization: Weill Cornell Medical College

kov9001@med.cornell.edu

2127462646

Study Officials

• Koen van Besien, MD, PhD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: December 10, 2012
• Study Start: October 26, 2012
• Primary Completion: April 29, 2015
• Study Completion: April 29, 2015
• Last Updated: July 11, 2018
• Results First Posted: August 9, 2017

Record last verified: 2018-05

Locations

US (1)