Combined Haploidentical-Cord Blood Transplantation for Adults and Children

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00943800
• Collaborator: (none)
• Enrollment: 87
• Location: 1
• Arms: 3
• Actual Duration (Months): 142.8
• Patients Per Site Per Month: 0.6

Study Details

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	N/A

Study Design

• Study Type: Interventional
• 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: Oct 9, 2006
• Actual Primary Completion Date: Sep 1, 2018
• Actual Study Completion Date: Sep 1, 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 [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) [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 [up to 5 years]

   We reported overall survival at 2 years and 5 years after transplant

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Dec 5, 2013

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00943800
• Other Study ID Numbers: 14736B
• First Posted: Jul 22, 2009
• Last Update Posted: Jan 27, 2021
• Last Verified: Jan 1, 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; Vidarabine; Fludarabine; Fludarabine phosphate; Melphalan; Busulfan; Thiotepa; Antilymphocyte Serum; Thymoglobulin

Study Results

Participant Flow

Arm/Group Title	Treatment Group
Arm/Group Description	Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m^2 of Fludarabine from Day-7 until Day-3, 140mg/m^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1."
Period Title: Overall Study
STARTED	87
COMPLETED	87
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment Group
Arm/Group Description	Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m^2 of Fludarabine from Day-7 until Day-3, 140mg/m^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1."
Overall Participants	87
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	45.5
Sex: Female, Male (Count of Participants)
Female	36 41.4%
Male	51 58.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.1%
Asian	3 3.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	21 24.1%
White	53 60.9%
More than one race	0 0%
Unknown or Not Reported	9 10.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Neutrophil Engraftment
Description	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.
Time Frame	Transplant (Day 0) through Day +28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description	Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m^2 of Fludarabine from Day-7 until Day-3, 140mg/m^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1."
Measure Participants	87
Number (95% Confidence Interval) [percentage of patients]	85.1

2. Secondary Outcome

Title	Percentage of Participants With Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD)
Description	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
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description	Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m^2 of Fludarabine from Day-7 until Day-3, 140mg/m^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1."
Measure Participants	87
Acute GVHD (grade II-IV)	16.1
Chronic GVHD	3.4

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment Group
Arm/Group Description	Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m^2 of Fludarabine from Day-7 until Day-3, 140mg/m^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1."
Measure Participants	87
Two-year overall survival	43.7
Five-year overall survival	32.9

Adverse Events

Time Frame	100 days
Arm/Group Title	Treatment Group
Arm/Group Description	Although the protocol initially had different disease intensities, ultimately, moved to one regimen for all patients. Subjects received 30mg/m^2 of Fludarabine from Day-7 until Day-3, 140mg/m^2 of Melphalan on Day-2, and 1.5mg/kg of Rabbit antithymocyte globulin at Day-7,-5,-3 and -1."
All Cause Mortality
	Treatment Group
	Affected / at Risk (%)	# Events
Total	18/87 (20.7%)
Serious Adverse Events
	Treatment Group
	Affected / at Risk (%)	# Events
Total	24/87 (27.6%)
Blood and lymphatic system disorders
Anemia	1/87 (1.1%)
Febrile neutropenia	1/87 (1.1%)
Cardiac disorders
Heart failure	1/87 (1.1%)
Pericardial tamponade	1/87 (1.1%)
Gastrointestinal disorders
Diarrhea	1/87 (1.1%)
Fever	1/87 (1.1%)
General disorders
Gait disturbance	1/87 (1.1%)
Immune system disorders
Cytokine release syndrome	1/87 (1.1%)
Infections and infestations
Abdominal infection	2/87 (2.3%)
Epstein-barr virus infection	3/87 (3.4%)
Esophageal infection	1/87 (1.1%)
Lung infection	2/87 (2.3%)
Sepsis	11/87 (12.6%)
Skin infection	1/87 (1.1%)
Investigations
Neutrophil count decreased	1/87 (1.1%)
White blood cell decreased	1/87 (1.1%)
Metabolism and nutrition disorders
Hypernatremia	1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/87 (3.4%)
Respiratory failure	4/87 (4.6%)
Other (Not Including Serious) Adverse Events
	Treatment Group
	Affected / at Risk (%)	# Events
Total	0/87 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.