The Rapid Study: Randomized Phase II Study To Expedite Allogeneic Transplant With Immediate Haploidentical Plus Unrelated Cord Donor Search Versus Matched Unrelated Donor Search For AML And High-Risk MDS Patients

• Sponsor: University of Chicago (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02648932
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arms: 2
• Actual Duration (Months): 49.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study seeks to compare time from formal search to hematopoietic cell transplantation (HCT) for patients 18 years and older, randomized between haplo-cord search and matched unrelated donor (MUD) search for patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS)

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)	Biological: Haplo-Cord Transplant; Procedure: Matched Unrelated Donor Transplant	Phase 2

Detailed Description

Primary Objectives

To compare time from formal search to hematopoietic cell transplantation (HCT) for patients 18 years and older, randomized between haplo-cord search and matched unrelated donor (MUD) search for patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS)

Secondary Objectives

• To compare the percentage of patients who undergo HCT in each study cohort

• To evaluate overall survival from time to randomization by study cohort

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Rapid Study: Randomized (RA) Phase (P) II Study To Expedite Allogeneic Transplant With Immediate (I) Haploidentical Plus Unrelated Cord Donor (D) Search Versus Matched Unrelated Donor Search For AML And High-Risk MDS Patients
• Actual Study Start Date: Feb 4, 2016
• Actual Primary Completion Date: Apr 1, 2020
• Actual Study Completion Date: Apr 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Haplo-Cord Search If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant.	Biological: Haplo-Cord Transplant; For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device
Other: Matched Unrelated Donor Search (MUD) If subject meets the inclusion criteria and consents, will undergo a MUD transplant.	Procedure: Matched Unrelated Donor Transplant

Outcome Measures

Primary Outcome Measures

1. Time to Transplant [Through one year after formal search]

   Time to transplant will be measured from time of date of formal request to stem cell infusion date. Will also capture time from preliminary search to both formal search and transplant date.

Secondary Outcome Measures

1. Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT) [Through one year after formal search]

   Compare percentage of patients who undergo HCT in each study cohort

2. Estimated Survival Time [From date of randomization up to 3 years]

   Overall survival time was estimated from date of randomization and from date of transplant using Kaplan-Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for Search Phase:

1. Diagnosis of acute myeloid leukemia (AML) or high or very high-risk MDS by international prognostic scoring system revised for whom transplant is recommended

2. 18 years of age or older

3. Subject is likely to be considered for allogeneic transplant in the opinion of the transplant physician (based on age of patient, health, cytogenetics, and/or molecular characteristics).

4. Karnofsky Performance Status (KPS) >/= 70% at time of enrollment. An exception will be made for those with lower KPS at enrollment with an acute worsening that is likely to resolve in the treating physicians judgment (e.g., reversible infection,trauma, medication reaction, etc)

5. Ability to understand and the willingness to sign a written informed consent document for the Search Phase.

6. Patient willing to consider HCT

7. A preliminary search has identified:

8. An appropriate minimum 4/6 matched umbilical cord unit at intermediate resolution at HLA-A and B, and high resolution at HLA-DRB with a cell dose above 1 x 10(7) TNC/kg for a single umbilical cord blood (UCB) transplant AND

9. At least one potential 8/8 HLA-matched (HLA-A, -B, -C, and -DRB1) unrelated donor with a probability of 70% AND

10. Availability of a potential related haploidentical donor.

Exclusion Criteria for Search Phase:

1. Prior formal search was instituted

2. Diagnosis of acute promyelocytic leukemia (APL)

3. Known HLA matched related donor without contraindications to donate

4. Life expectancy severely limited by concomitant illness or uncontrolled infection

Inclusion Criteria for Transplant Phase

1. High-risk AML for which transplant is recommend based on cytogenetic, molecular and morphologic features. Patients must meet institutional standards for disease control prior to transplant.

2. For MDS. IPSS-revised criteria of high or very high at diagnosis.

3. Subject meets institutional criteria for transplant and has acceptable organ and marrow function as defined below:

4. Serum bilirubin < 2.0mg/dL unless Gilberts disease

5. Creatinine Clearance > 45 mL/min.1.73m2 as estimated by modified MDRD equation

6. Left ventricular function 40% or greater

7. DLCO corrected for hemoglobin >50%

8. KPS 70% or greater

9. An adequate graft for the defined donor type

10. Haplo-cord requires a haploidentical adult donor of 14 years of age and at least 50 kg, and a cord blood unit with at least 1.0 x 10(7) TNC/kg and a match of at least 4/6 by intermediate resolution for HLA-A and B and high resolution at DRB1. Donor provides standard of care consent for harvest following institutional policy. Any donor samples or donor research data would be obtained on separate donor research protocol.

11. For MUD requires a 7/8 or 8/8 HLA matched unrelated donor with high resolution matching at HLA-A, -B, -C, and DRB1. DP matching or DP permissive should be achieved when possible using T-cell epitope strategy.

12. Written informed consent for the transplant phase

Exclusion Criteria for Transplant Phase

1. Life expectancy severely limited by concomitant illness or uncontrolled infection

2. HIV-positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Cancer Center	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

• Principal Investigator: Andrew Artz, MD, University of Chicago

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2015

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT02648932
• Other Study ID Numbers: IRB15-0866
• First Posted: Jan 7, 2016
• Last Update Posted: Mar 18, 2021
• Last Verified: Feb 1, 2021

• Keywords provided by University of Chicago: Acute Myeloid Leukemia (AML); High-Risk Myelodysplastic Syndrome (MDS); hematopoietic cell transplantation; haplo-cord search; matched unrelated donor search
• Additional relevant MeSH terms: Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes

Study Results

Participant Flow

Arm/Group Title	Haplo-Cord Search	Matched Unrelated Donor Search (MUD)
Arm/Group Description	If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device	If subject meets the inclusion criteria and consents, will undergo a MUD transplant. Matched Unrelated Donor Transplant
Period Title: Overall Study
STARTED	5	4
COMPLETED	2	3
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Haplo-Cord Search	Matched Unrelated Donor Search (MUD)	Total
Arm/Group Description	If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device	If subject meets the inclusion criteria and consents, will undergo a MUD transplant. Matched Unrelated Donor Transplant	Total of all reporting groups
Overall Participants	5	4	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67.9	61.2	62.1
Sex: Female, Male (Count of Participants)
Female	2 40%	3 75%	5 55.6%
Male	3 60%	1 25%	4 44.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 20%	0 0%	1 11.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 25%	1 11.1%
White	3 60%	2 50%	5 55.6%
More than one race	1 20%	0 0%	1 11.1%
Unknown or Not Reported	0 0%	1 25%	1 11.1%

Outcome Measures

1. Primary Outcome

Title	Time to Transplant
Description	Time to transplant will be measured from time of date of formal request to stem cell infusion date. Will also capture time from preliminary search to both formal search and transplant date.
Time Frame	Through one year after formal search

Outcome Measure Data

Analysis Population Description

We analyze only those who went to transplant.

Arm/Group Title	Haplo-Cord Search	Matched Unrelated Donor Search (MUD)
Arm/Group Description	If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device	If subject meets the inclusion criteria and consents, will undergo a MUD transplant. Matched Unrelated Donor Transplant
Measure Participants	2	3
Median (Full Range) [days]	69	111

2. Secondary Outcome

Title	Percentage of Patients Who Undergo Hematopoietic Cell Transplantation (HCT)
Description	Compare percentage of patients who undergo HCT in each study cohort
Time Frame	Through one year after formal search

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Haplo-Cord Search	Matched Unrelated Donor Search (MUD)
Arm/Group Description	If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device	If subject meets the inclusion criteria and consents, will undergo a MUD transplant. Matched Unrelated Donor Transplant
Measure Participants	5	4
Count of Participants [Participants]	2 40%	3 75%

3. Secondary Outcome

Title	Estimated Survival Time
Description	Overall survival time was estimated from date of randomization and from date of transplant using Kaplan-Meier method.
Time Frame	From date of randomization up to 3 years

Outcome Measure Data

Analysis Population Description

We analyzed only those who went transplant.

Arm/Group Title	Haplo-Cord Search	Matched Unrelated Donor Search (MUD)
Arm/Group Description	If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device	If subject meets the inclusion criteria and consents, will undergo a MUD transplant. Matched Unrelated Donor Transplant
Measure Participants	2	3
Days from randomization	162	785
Days from transplant	92	673

Adverse Events

Time Frame	100 days
Arm/Group Title	Haplo-Cord Search		Matched Unrelated Donor Search (MUD)
Arm/Group Description	If subject meets the inclusion criteria and consents, will undergo a haplo-cord transplant. Haplo-Cord Transplant: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device		If subject meets the inclusion criteria and consents, will undergo a MUD transplant. Matched Unrelated Donor Transplant
All Cause Mortality
	Haplo-Cord Search		Matched Unrelated Donor Search (MUD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/3 (66.7%)
Serious Adverse Events
	Haplo-Cord Search		Matched Unrelated Donor Search (MUD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Haplo-Cord Search		Matched Unrelated Donor Search (MUD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		2/3 (66.7%)
Blood and lymphatic system disorders
Anemia	1/2 (50%)		2/3 (66.7%)
Cardiac disorders
Sinus tachycardia	0/2 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Diarrhea	1/2 (50%)		2/3 (66.7%)
Nausea	1/2 (50%)		1/3 (33.3%)
Abdominal pain	0/2 (0%)		2/3 (66.7%)
Dry mouth	0/2 (0%)		1/3 (33.3%)
Oral hemorrhage	0/2 (0%)		1/3 (33.3%)
Oral pain	0/2 (0%)		1/3 (33.3%)
Vomiting	0/2 (0%)		2/3 (66.7%)
General disorders
Fatigue	1/2 (50%)		1/3 (33.3%)
Chills	0/2 (0%)		1/3 (33.3%)
Fever	0/2 (0%)		1/3 (33.3%)
Investigations
Weight loss	1/2 (50%)		0/3 (0%)
White blood cell decreased	1/2 (50%)		1/3 (33.3%)
Metabolism and nutrition disorders
Anorexia	0/2 (0%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/2 (0%)		1/3 (33.3%)
Myalgia	0/2 (0%)		1/3 (33.3%)
Nervous system disorders
Tremor	0/2 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/2 (50%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Purpura	1/2 (50%)		0/3 (0%)
Rash maculo-papular	0/2 (0%)		1/3 (33.3%)
Vascular disorders
Hypertension	0/2 (0%)		1/3 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.