Trial Outcomes & Findings for A Two-Step Approach to Bone Marrow Transplant Using Cells From Two Partially-Matched Relatives (NCT NCT01532635)

NCT ID: NCT01532635

Last Updated: 2025-05-04

Results Overview

To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

4 participants

Primary outcome timeframe

1 year

Results posted on

2025-05-04

Participant Flow

Participant milestones

Participant milestones
Measure
Allogeneic HSCT Using Two Related Donors
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Overall Study
STARTED
4
Overall Study
COMPLETED
4
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Two-Step Approach to Bone Marrow Transplant Using Cells From Two Partially-Matched Relatives

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Allogeneic HSCT Using Two Related Donors
n=4 Participants
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Age, Continuous
50.35 years
STANDARD_DEVIATION 20.64 • n=5 Participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
Sex: Female, Male
Male
2 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
4 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
4 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Region of Enrollment
United States
4 participants
n=5 Participants

PRIMARY outcome

Timeframe: 1 year

To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

To assess chimerism to ascertain whether one donor is emerging as dominant at regular intervals beginning at the time of engraftment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

If dominance is observed, to compare the 2 donors with regard to degree of HLA mismatch, KIR types, CD 34+ cell doses, infusion order, donor age, and donor alloreactivity points in an effort to identify potential biologic factors that predict for dominance. To determine if trends toward dominance occur in T cell, NK cell, or other cellular subsets prior to emerging in the graft as a whole.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

To assess if establishment of a dominant donor versus persistent chimerism of both donors is associated with a lower relapse rate.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

To assess the consistency and pace of engraftment of both donors.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Assess T and B cell Reconstitution

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Assessment of regimen related toxicity, GVHD incidence and severity, and overall survival.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2-6 days prior to transplant

Assessment of the tolerance of the period of fever, diarrhea, and rash after the introduction of second donor and qualitatively compare it to prior patient groups or concurrent patient groups

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year post transplant

To test for loss of one or both HLA haplotypes in patients who relapse post-transplant and examine the relapse in the context of the characteristics of the 2 donors

Outcome measures

Outcome data not reported

Adverse Events

Allogeneic HSCT Using Two Related Donors

Serious events: 3 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Allogeneic HSCT Using Two Related Donors
n=4 participants at risk
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
Respiratory, thoracic and mediastinal disorders
Dyspnea
25.0%
1/4 • Number of events 1
General disorders
Fevers
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Hyperbilirubinemia
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Hypoxia
25.0%
1/4 • Number of events 1
Cardiac disorders
Left ventricular systolic dysfunction
25.0%
1/4 • Number of events 1
Cardiac disorders
Pericardial effusion
25.0%
1/4 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
25.0%
1/4 • Number of events 1
General disorders
Dehydration
25.0%
1/4 • Number of events 1

Other adverse events

Other adverse events
Measure
Allogeneic HSCT Using Two Related Donors
n=4 participants at risk
CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.
General disorders
Abdominal pain
50.0%
2/4 • Number of events 4
Psychiatric disorders
Anxiety
50.0%
2/4 • Number of events 2
General disorders
Arm pain
25.0%
1/4 • Number of events 1
Cardiac disorders
Atrial fibrillation
25.0%
1/4 • Number of events 1
General disorders
Back pain
50.0%
2/4 • Number of events 2
Blood and lymphatic system disorders
Bacteremia
25.0%
1/4 • Number of events 1
General disorders
Balance problems
25.0%
1/4 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Bronchitis
25.0%
1/4 • Number of events 1
Eye disorders
Change in vision
25.0%
1/4 • Number of events 1
General disorders
Chest pain
75.0%
3/4 • Number of events 4
General disorders
Chest tightness
25.0%
1/4 • Number of events 1
General disorders
Chills
50.0%
2/4 • Number of events 2
Gastrointestinal disorders
Clostridium difficile
25.0%
1/4 • Number of events 1
Immune system disorders
CMV reactivation
50.0%
2/4 • Number of events 2
Gastrointestinal disorders
Constipation
50.0%
2/4 • Number of events 4
Renal and urinary disorders
Decreased urine output
50.0%
2/4 • Number of events 4
General disorders
Dehydration
25.0%
1/4 • Number of events 1
Psychiatric disorders
Depression
25.0%
1/4 • Number of events 1
Gastrointestinal disorders
Diarrhea
100.0%
4/4 • Number of events 9
General disorders
Dizziness
25.0%
1/4 • Number of events 1
General disorders
Dry eyes
25.0%
1/4 • Number of events 1
Gastrointestinal disorders
Dyspepsea
25.0%
1/4 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Dyspnea
50.0%
2/4 • Number of events 2
Renal and urinary disorders
Dysuria
50.0%
2/4 • Number of events 4
Skin and subcutaneous tissue disorders
Edema
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Electrolyte imbalance
75.0%
3/4 • Number of events 3
General disorders
Fatigue
50.0%
2/4 • Number of events 2
General disorders
Feet pain
25.0%
1/4 • Number of events 1
General disorders
Fevers
100.0%
4/4 • Number of events 11
Blood and lymphatic system disorders
Fluid overload
50.0%
2/4 • Number of events 3
General disorders
Generalized pain
50.0%
2/4 • Number of events 2
General disorders
Generalized weakness
25.0%
1/4 • Number of events 1
Skin and subcutaneous tissue disorders
GVHD rash
25.0%
1/4 • Number of events 1
General disorders
Hand pain
25.0%
1/4 • Number of events 1
General disorders
Headache
75.0%
3/4 • Number of events 3
Gastrointestinal disorders
Heartburn
50.0%
2/4 • Number of events 2
Renal and urinary disorders
Hematuria
50.0%
2/4 • Number of events 2
Blood and lymphatic system disorders
HHV-6 reactivation
25.0%
1/4 • Number of events 1
General disorders
Hiccups
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Hyperbilirubinemia
100.0%
4/4 • Number of events 6
Blood and lymphatic system disorders
Hypertension
50.0%
2/4 • Number of events 3
Blood and lymphatic system disorders
Hypokalemia
25.0%
1/4 • Number of events 2
Blood and lymphatic system disorders
Hyponatremia
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Hypotension
75.0%
3/4 • Number of events 5
General disorders
Hypothermia
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Hypoxia
50.0%
2/4 • Number of events 3
General disorders
Increased alkaline phosphatase
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Increased creatinine
75.0%
3/4 • Number of events 4
Hepatobiliary disorders
Increased LFTs
25.0%
1/4 • Number of events 1
General disorders
Knee pain
25.0%
1/4 • Number of events 1
General disorders
Leg pain
25.0%
1/4 • Number of events 1
Metabolism and nutrition disorders
Malnutrition
25.0%
1/4 • Number of events 1
Psychiatric disorders
Mental status change
25.0%
1/4 • Number of events 1
Gastrointestinal disorders
Mucositis
100.0%
4/4 • Number of events 4
General disorders
Neck pain
25.0%
1/4 • Number of events 1
Renal and urinary disorders
Nocturia
50.0%
2/4 • Number of events 2
Blood and lymphatic system disorders
Orthostatic hypotension
50.0%
2/4 • Number of events 2
Musculoskeletal and connective tissue disorders
Osteopenia
25.0%
1/4 • Number of events 1
General disorders
Parotitis
25.0%
1/4 • Number of events 1
Blood and lymphatic system disorders
Platelet transfusion reaction
25.0%
1/4 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Pneumonitis
50.0%
2/4 • Number of events 2
Skin and subcutaneous tissue disorders
Pruritus
25.0%
1/4 • Number of events 1
Skin and subcutaneous tissue disorders
Rash
100.0%
4/4 • Number of events 9
General disorders
Rectal pain
25.0%
1/4 • Number of events 1
General disorders
Rigors
25.0%
1/4 • Number of events 1
General disorders
Shoulder pain
25.0%
1/4 • Number of events 1
General disorders
Swollen ankles
25.0%
1/4 • Number of events 1
Cardiac disorders
Tachycardia
50.0%
2/4 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Tachypnea
25.0%
1/4 • Number of events 1
General disorders
Toenail bleeding
25.0%
1/4 • Number of events 1
General disorders
Trouble sleeping
50.0%
2/4 • Number of events 2
General disorders
Upper extremity swelling
25.0%
1/4 • Number of events 1
Renal and urinary disorders
Urinary retention
50.0%
2/4 • Number of events 2
General disorders
Vaginal discomfort/itching
25.0%
1/4 • Number of events 1
Cardiac disorders
Volume overload
25.0%
1/4 • Number of events 1
General disorders
Weight loss
25.0%
1/4 • Number of events 1

Additional Information

Neal Flomenberg, MD

Thomas Jefferson University

Phone: 215-955-8874

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place