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

Tracking Information

• First Submitted Date: July 20, 2009
• First Posted Date: July 22, 2009
• Results First Submitted Date: October 5, 2020
• Results First Posted Date: October 27, 2020
• Last Update Posted Date: January 27, 2021
• Actual Study Start Date: October 9, 2006
• Actual Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 8, 2021)

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.

• Original Primary Outcome Measures (submitted: July 21, 2009): To assess the rate of engraftment with combined haploidentical-cord blood [ Time Frame: 5 years ]

Current Secondary Outcome Measures (submitted: January 8, 2021)

• 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
• 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

• Original Secondary Outcome Measures (submitted: July 21, 2009): To assess the rates of GVHD with combined haploidentical-cord blood (acute & chronic) [ Time Frame: 5 years ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Combined Haploidentical-Cord Blood Transplantation for Adults and Children
• Official Title: Combined Haploidentical-Cord Blood Transplantation for Adults and Children
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Leukemia
• Myelodysplastic Syndrome
• Multiple Myeloma
• Lymphoma

Intervention

• 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.
• 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.
• 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.

Study Arms

• Experimental: Good Risks patients
  For patients transplanted in remission.
  Interventions:

  • Drug: Fludarabine-Melphalan & Rabbit antithymocyte globulin (r-ATG)
  • Procedure: Stem Cell Transplant
  • Procedure: Stem Cells Collections
• Experimental: High Risk Patients eligible for radiation
  Interventions:

  • Procedure: Stem Cell Transplant
  • Procedure: Stem Cells Collections
  • Drug: Fludarabine, Thiotepa, Antithymocyte globulin (ATG), and Total Body Irradiation (TBI)
• Experimental: High Risk Patients not eligible for radiation
  Interventions:

  • Procedure: Stem Cell Transplant
  • Procedure: Stem Cells Collections
  • Drug: Fludarabine, Busulfan, and ATG

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 5, 2020): 87
• Original Estimated Enrollment (submitted: July 21, 2009): 53
• Actual Study Completion Date: September 2018
• Actual Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00943800
• Other Study ID Numbers: 14736B
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Chicago
• Study Sponsor: University of Chicago
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Chicago
• Verification Date: January 2021