Combined Haploidentical-Cord Blood Transplantation for Adults and Children

• ClinicalTrials.gov Identifier: NCT00943800
• Recruitment Status: Completed
• First Posted: July 22, 2009
• Results First Posted: October 27, 2020
• Last Update Posted: January 27, 2021
• Sponsor: University of Chicago
• Information provided by (Responsible Party): University of Chicago

Study Description

Brief Summary:

The primary objective is to assess the rate of engraftment with combined haploidentical-cord blood transplantation. The secondary objective is to evaluate the incidence and severity of acute and chronic graft-versus-host disease (GVHD).

Condition or disease	Intervention/treatment	Phase
Leukemia; Myelodysplastic Syndrome; Multiple Myeloma; Lymphoma	Drug: Fludarabine-Melphalan & Rabbit antithymocyte globulin (r-ATG); Procedure: Stem Cell Transplant; Procedure: Stem Cells Collections; Drug: Fludarabine, Thiotepa, Antithymocyte globulin (ATG), and Total Body Irradiation (TBI); Drug: Fludarabine, Busulfan, and ATG	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 87 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combined Haploidentical-Cord Blood Transplantation for Adults and Children
• Actual Study Start Date: October 9, 2006
• Actual Primary Completion Date: September 2018
• Actual Study Completion Date: September 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Good Risks patients; For patients transplanted in remission.	Drug: Fludarabine-Melphalan & Rabbit antithymocyte globulin (r-ATG); Fludarabine is given through the vein daily for 5 days. Melphalan is given through the vein daily for 2 days. ATG is given every day in the vein for four days.; Procedure: Stem Cell Transplant; Infusion of haploidentical donor, umbilical cord blood; Procedure: Stem Cells Collections; Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.
Experimental: High Risk Patients eligible for radiation	Procedure: Stem Cell Transplant; Infusion of haploidentical donor, umbilical cord blood; Procedure: Stem Cells Collections; Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.; Drug: Fludarabine, Thiotepa, Antithymocyte globulin (ATG), and Total Body Irradiation (TBI); Fludarabine is given through the vein daily for 5 days. Thiotepa is given through the vein daily for 2 days. ATG is given through the vein every other day for 4 days. TBI is given twice a day for 3 days.
Experimental: High Risk Patients not eligible for radiation	Procedure: Stem Cell Transplant; Infusion of haploidentical donor, umbilical cord blood; Procedure: Stem Cells Collections; Haploidentical cells will be T-cell depleted using the Miltenyi Clinimax device.; Drug: Fludarabine, Busulfan, and ATG; Fludarabine is given through the vein daily for 5 days. Busulfan is given through the vein daily for 4 days. ATG is given through the vein every other day for 4 days.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Neutrophil Engraftment [ Time Frame: Transplant (Day 0) through Day +28 ]
   Cumulative incidence of graft failure (neutrophil) by day 28 was reported. Patients who did not have neutrophil engraftment before death was considered as a competing risk. Failure to engraft was defined as lack of evidence of hematopoietic recovery (ANC <500/mm3 and platelet count < 20,000/mm3) by day +35, confirmed by a biopsy revealing a marrow cellularity < 5%. Graft failure was also defined as initial myeloid engraftment by day +35, documented to be of donor origin, followed by a drop in the ANC to < 500/mm3 for more than three days, independent of any myelosuppressive drugs, severe GVHD, CMV, or other infection.

Secondary Outcome Measures :

1. Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD) [ Time Frame: Up to 2 years ]

   Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

   Chronic GVHD is assessed by NIH consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria. (See Citation: Filipovich AH et al)

   The incidence of patients with acute GVHD (Grade II-IV) was determined at 180 days. The incidence of Chronic GVHD by 2 years was reported

2. Overall Survival- Percentage of Participants Who Survived at 2 Years and 5 Years [ Time Frame: up to 5 years ]
   We reported overall survival at 2 years and 5 years after transplant

Eligibility Criteria

• Ages Eligible for Study: 1 Year and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patients will be eligible for this study if they have any one of the diseases that are known to be cured after allogeneic stem cell transplantation.

1. Relapsed or refractory acute leukemia (myeloid or lymphoid)
2. Acute leukemia in first remission at high-risk for recurrence
3. Chronic myelogenous leukemia in accelerated phase or blast-crisis
4. Chronic myelogenous leukemia in chronic phase
5. Recurrent or refractory malignant lymphoma or Hodgkin lymphoma
6. Chronic lymphocytic leukemia, relapsed or with poor prognostic features
7. Multiple myeloma
8. Myelodysplastic syndrome
9. Chronic myeloproliferative disease
10. Hemoglobinopathies
11. Aplastic anemia

Exclusion Criteria:

1. Zubrod performance status > 2
2. Life expectancy is severely limited by concomitant illness
3. Patients with severely decreased LVEF or impaired pulmonary function tests(PFT's)
4. Estimated Creatinine Clearance <50 ml/min
5. Serum bilirubin> 2.0 mg/dl or SGPT >3 x upper limit of normal
6. Evidence of chronic active hepatitis or cirrhosis
7. HIV-positive
8. Patient is pregnant
9. Patient or guardian not able to sign informed consent

Contacts and Locations

Locations

United States, Illinois

The University of Chicago

Chicago, Illinois, United States, 60637

Sponsors and Collaborators

University of Chicago

Investigators

• Principal Investigator: Hongtao Liu, M.D.; University of Chicago

  Study Documents (Full-Text)

Documents provided by University of Chicago:

Study Protocol and Statistical Analysis Plan  [PDF] December 5, 2013

More Information

Publications of Results:

Liu H, Rich ES, Godley L, Odenike O, Joseph L, Marino S, Kline J, Nguyen V, Cunningham J, Larson RA, del Cerro P, Schroeder L, Pape L, Stock W, Wickrema A, Artz AS, van Besien K. Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions. Blood. 2011 Dec 8;118(24):6438-45. doi: 10.1182/blood-2011-08-372508. Epub 2011 Oct 5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00943800
• Other Study ID Numbers: 14736B
• First Posted: July 22, 2009
• Results First Posted: October 27, 2020
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

Keywords provided by University of Chicago:

Appropriate candidate for transplantation; An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.

Additional relevant MeSH terms:

Multiple Myeloma; Myelodysplastic Syndromes; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Vidarabine; Fludarabine; Fludarabine phosphate; Melphalan; Busulfan; Thiotepa; Antilymphocyte Serum; Thymoglobulin; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors