Partially HLA Mismatched (Haploidentical) Allogeneic Bone Marrow Transplantation

NCT01749293 | Terminated Phase 2 Results DMC

• 1 other identifier: 2012-0170
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic stem cell transplantation is a potentially curative treatment for patients with many hematologic malignancies (e.g. leukemia, lymphoma, and myeloma with high risk of relapse). This process requires a suitable donor. The best case scenario involves an Human Leukocyte Antigen (HLA) matched sibling donor. However, this type of donor is not always available. Donor registries can provide another source for matched unrelated donors, but this may take valuable time delaying treatment for the transplant recipient. Donor availability remains a significant barrier to the use of allogeneic (from a donor) stem cell transplant. This issue disproportionately affects patients of minority backgrounds. Novel strategies to improve outcomes using alternative donors are desperately needed. Haploidentical transplants are an alternative which provides a readily available donor in the form of a partially HLA matched family member. This provides for more potential donors and the donors can be selected based on other factors that can play a role in transplant success (e.g. age, gender, KIR alloreactivity). Recent advances in transplant techniques have greatly improved success rates with haploidentical transplants although disease relapse has remained as issue. This trial aims to provide an alternative transplant option for patients with hematologic malignancies who require bone marrow transplantation but lack an HLA identical donor. The investigational component of this study is the combination of the Fludarabine/ Busulfan/ Total Body Irradiation conditioning regimen and the HLA Haploidentical Transplant with post-transplant Cyclophosphamide.

Conditions

Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• Number of Participants That Engrafted and the Number of Participants That Had Full Donor Chimerism at Day 60

  To estimate the number of participants that had engraftment rates and the number of participants that had full donor chimerism at Day 60 in patients undergoing an HLA haploidentical stem cell transplant with post transplant high dose cyclophosphamide.

  Up to Day 60 post-transplant.

Secondary Outcomes (2)

• Number of Participants That Had an Overall Survival Rate

  Up to one year post-transplant.

• Number of Participants That Had an Event Free Survival Rate

  Up to 1 year post-transplant

Study Arms (1)

Haploidentical Transplant

EXPERIMENTAL

All subjects will be dosed with pre-transplant Fludarabine (180mg/m2)and Busulfan total AUC 2400 μmol\*min/L or 6.4mg/kg. Subjects will then undergo total body irradiation 2Gy. Subjects will undergo haploidentical allogeneic bone marrow transplant, followed by Cyclophosphamide, Tacrolimus and MMF based GVHD prophylaxis.

Procedure: Haploidentical Transplant; Drug: Fludarabine; Drug: Busulfan; Radiation: Total Body Irradiation; Drug: Cyclophosphamide

Interventions

Haploidentical Transplant PROCEDURE

Subjects will be dosed with pre-transplant Fludarabine (180mg/m2)and Busulfan total AUC 2400 μmol\*min/L or 6.4mg/kg. Subjects will then undergo total body irradiation 2Gy. Subjects will undergo haploidentical allogeneic bone marrow transplant, followed by Cyclophosphamide, Tacrolimus and MMF based GVHD prophylaxis.

Also known as: Mismatched allogeneic bone marrow transplant

Haploidentical Transplant

Fludarabine DRUG

Subjects in this trial will receive Fludarabine 30 mg/m2 IV QD, adjusted for CrCl from Days -8 through -3.

Also known as: Fludara

Haploidentical Transplant

Busulfan DRUG

Subjects in this trial will receive Busulfan total AUC 2400 μmol\*min/L or 6.4mg/kg in 4 doses with seizure prophylaxis from Days -6 through -3.

Also known as: Busulfex, Myleran

Haploidentical Transplant

Total Body Irradiation RADIATION

Subjects in this trial will receive total body irradiation (2Gy fractionated) from Day -2 or -1.

Haploidentical Transplant

Cyclophosphamide DRUG

Subjects in this trial will receive Cyclophosphamide 50 mg/kg IV QD on Days 3 and 4 post-transplant.

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Haploidentical Transplant

Eligibility Criteria

• Age: 10 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• First-degree related donor or half-sibling who is at minimum HLA haploidentical
• Lack of fully matched donor (related or unrelated). Patients with a matched unrelated donor may only be enrolled if they require an urgent transplant. Urgency of transplant will judged by PI and co-investigators.
• Eligible diagnoses are listed below:
• Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed during multiagent therapy including follicular lymphoma, Marginal zone (or MALT) lymphoma, lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia, Hairy cell leukemia, Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL), Prolymphocytic leukemia, Multiple myeloma and Plasma cell leukemia
• Poor-risk SLL or CLL
• Aggressive lymphoma that has failed at least one prior regimen of multiagent chemotherapy, and patient is either ineligible for autologous BMT or autologous BMT is not recommended including Hodgkin lymphoma, high grade Follicular lymphoma, Mantle cell lymphoma, Diffuse large B-cell lymphoma, Burkitt's lymphoma/leukemia, Anaplastic large cell lymphoma, Plasmablastic lymphoma, Peripheral T-cell lymphoma
• Relapsed or refractory acute leukemias.
• Poor-risk acute leukemia in first remission:
• i. Acute myeloid leukemia (AML) with at least one of the following:
• AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative disorder
• Presence of FLT3 internal tandem duplications
• Poor-risk cytogenetics
• ii. Acute lymphoblastic leukemia and/or lymphoma (ALL) with at least one of the following:
• Poor risk cytogenetics
• Primary refractory disease

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

fludarabine; fludarabine phosphate; Busulfan; Whole-Body Irradiation; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Pritesh Patel
• Organization: University of Illinois

prpatel8@uic.edu

312-996-5762

Study Officials

• Pritesh Patel, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Faculty, Asst. Professor

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: December 13, 2012
• Study Start: August 30, 2012
• Primary Completion: May 15, 2014
• Study Completion: May 15, 2014
• Last Updated: February 25, 2020
• Results First Posted: February 25, 2020

Record last verified: 2020-02

Locations

US (1)