Hematopoietic Stem Cell Transplantation (HSCT) Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit

NCT01050946 | Terminated Phase 2 Results DMC

• 1 other identifier: MCW 11491
• Study Type: interventional
• Target: 1
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a means of providing transplantation to those patients who would be a stem cell transplant candidate who do not have an appropriate donor. The use of CD34 selected haploidentical donor with an umbilical cord unit may help provide earlier engraftment without the need for long term immunosuppression. This study tests a new method of bone marrow transplantation called combined haploidentical-cord blood transplantation. In this procedure, some of the blood forming cells (the stem cells) from a partially human leukocyte antigen (HLA) matched (haploidentical) related donor are collected from the blood, as well as cells from an umbilical cord are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow).

Conditions

Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Chronic; Leukemia, Myelocytic, Acute; Leukemia, Myeloid, Chronic; Lymphoma, Non-Hodgkin; Lymphoma, Hodgkins

Keywords

Unrelated Umbilical Cord Blood Transplant(UCB); CD34+ Selected mismatched related donor; Haploidentical donor; hematopoietic stem cell transplantation(HSCT); ALL; Leukemia, Lymphocytic, Acute; AML; Leukemia, Myelocytic, Acute; CML; Leukemia, Myeloid, Chronic; NHL; Lymphoma, Non-Hodgkin; HL; Lymphoma, Hodgkins

Outcome Measures

Primary Outcomes (1)

• The Primary Objective is to Estimate the Overall Survival, Separately in the Two Risk Strata.

  3 years

Secondary Outcomes (6)

• Time to Relapse: To Assess the Incidence of Acute Leukemia or Lymphoma Relapse From Day of Transplant

  2 years

• Time to Neutrophil Engraftment: To Assess the Incidence of Neutrophil Engraftment From Day of Transplant

  100 days

• Time to Platelet Engraftment: To Assess the Incidence of Platelet Engraftment From Day of Transplant,

  100 days

• Time to Acute GVHD: We Will Assess the Incidence and Severity of Grades II-IV and Grades III-IV Acute GVHD From Day of Transplant.

  100 days

• Transplant Related Mortality (TRM): TRM is Death Occurring in Patients in Continuous Complete Remission.

  1 year

Study Arms (1)

Haploidentical/cord transplant

OTHER

Haploidentical/cord transplant with the precondition regimen at discretion of treating physician.

Biological: Haploidentical/cord transplant

Interventions

Haploidentical/cord transplant BIOLOGICAL

Myeloablative preparative regimen of chemotherapy and radiation followed by mismatch related(haploidentical)donor and one unit umbilical cord blood transplantation. Conditioning Regimens Choice of regimen at the discretion of the treating physician 1. Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG 1.5mg/m2(Day-7,-5,-3,-1) 2. Fludarabine 50mg/m2(Day -6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2),400cGY Total Body Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1) Day 0 -Haploidentical donor and one umbilical cord blood unit infusion

Also known as: Cord Blood Transplant

Haploidentical/cord transplant

Eligibility Criteria

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

You may qualify if:

• Patients between 18 and 65 years old
• Patient has a related family member(haploidentical) or unrelated which is 5 of 10 HLA identical match.
• Standard Risk
• Acute myelogenous leukemia: CR1 with high risk cytogenetics or molecular abnormalities such as FLT-3 ITD, or CR2 with a first remission that must have lasted \> 1 year.
• Acute Lymphocytic Leukemia: CR1, in order to be standard risk must NOT have Philadelphia Chromosome.
• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory to fludarabine or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog).
• Chronic myelogenous leukemia: resistant to or intolerant of TKI, in CP1 or CP2, or with a mutation that suggests resistance to TKI.
• Myelodysplastic Syndrome: RA, RARS, must be IPSS ≥ INT-2, Blasts \<5%.
• High Risk Patients:
• Acute myelogenous leukemia: Patients with CR2 are considered high risk if they have high risk cytogenetics, or molecular abnormalities or CR1 lasted for less than 1 year. Any evidence of active disease or no blasts in an acellular marrow.
• Acute Lymphocytic Leukemia: CR1- with Ph+ disease, CR2/+ with any cytogenetics. Any evidence of active disease.
• Chronic myelogenous leukemia- CP2/+, AP1/+, resistant or intolerant to TKI.
• Hodgkin's or Non Hodgkin's lymphoma- Disease recurrence following an autologous transplant, or high risk disease not thought to benefit from autologous transplant.
• Chronic lymphocytic leukemia- that is resistant to fludarabine, and never has been in remission or with stable disease/progressive disease
• Multiple myeloma: Must have had prior treatment. Patients in CR2 or greater can be considered, must have already failed autologous transplant Previous autologous transplant,must have been greater than 6 months prior to undergoing this transplant.

You may not qualify if:

• Patients \<18 years old Disease related criteria
• APML, presence of t(15,17) in first CR
• Patients with good risk AML, for example t(8;21), or inv 16, or normal cytogenetics with FLT-3-ITD negative, NPM-1 positive disease in 1st CR
• MDS IPSS \< INT-2 Miscellaneous Criteria
• Recipients who have a matched related sibling or unrelated donor
• If recipient has evidence of anti-HLA antibodies directed against cord or haplo-donor as determined byflowPRA.
• Underlying health criteria:
• Zubrod performance status \> 2 (see Appendix E)
• Life expectancy is limited to less than 8 weeks by concomitant illness
• Patients with severely decreased LVEF (EF \< 40%)
• Impaired pulmonary function tests (PFT's) (FVC, FEV1, DLCO \< 45% predicted)
• Estimated Creatinine Clearance \<50 ml/min
• Serum bilirubin\> 2.0 mg/dl or SGPT \>3 x upper limit of normal
• Evidence of chronic active hepatitis or cirrhosis
• HIV-positive

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Related Publications (1)

• 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

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Hodgkin Disease

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Lymphoma

Results Point of Contact

• Title: Jeanne Palmer,MD
• Organization: Medical College of Wisconsin

jpalmer@mcw.edu

414-805-6800

Study Officials

• Jeanne Palmer, M.D.

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Professor of Medicine

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 18, 2010
• Study Start: July 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: November 20, 2015
• Results First Posted: September 25, 2015

Record last verified: 2015-10