Trial Outcomes & Findings for Stem Cell Transplantation for Metastatic Solid Tumors (NCT NCT00001880)

Last Updated: 2021-11-10

Results Overview

To identify an anti-tumor effect of allogenic PNSC transplantation by induction of a graft-versus-tumor (GVT) effect in patients with a diversity of metastatic solid tumors, which are refractory to standard therapy. Tumor response assessed as follows: Complete response (CR): disappearance of all signs and symptoms of metastatic disease for a period of at least one month. Partial response (PR): a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month. No new metastatic lesions may appear. Stable disease (SD): tumor measurements not meeting the criteria of CR, PR, or PD. Progressive disease (PD): increase of 25% or greater in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the development of any new metastatic disease.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

one year

Results posted on

2021-11-10

Participant Flow

Study was closed early due to lack of accrual

Participant milestones

Participant milestones
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Overall Study STARTED	42
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Overall Study Death	14

Baseline Characteristics

22 male participants and 20 female participants for total of 42 participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=42 Participants CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Age, Continuous Male	55 years n=22 Participants • 22 male participants and 20 female participants for total of 42 participants
Age, Continuous Female	45 years n=20 Participants • 22 male participants and 20 female participants for total of 42 participants
Sex: Female, Male Female	20 Participants n=42 Participants
Sex: Female, Male Male	22 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=42 Participants
Race (NIH/OMB) Asian	0 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	3 Participants n=42 Participants
Race (NIH/OMB) White	37 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=42 Participants
Region of Enrollment United States	42 participants n=42 Participants

PRIMARY outcome

Timeframe: one year

Outcome measures

Outcome measures
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=42 Participants CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect. Complete response (CR)	0 Participants
Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect. Partial response (PR)	9 Participants
Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect. Stable disease (SD):	5 Participants
Number of Participants Based on Tumor Response Criteria With Anti-tumor Effect Induce by Graft-versus-tumor Effect. Progressive disease (PD)	28 Participants

SECONDARY outcome

Timeframe: Day 100

Population: 9 participants data was not evaluable

Number of participants that achieved engraftment based on blood Chimerism Cluster of differentiation 3 (CD3) analysis that is greater than or equal to 95%.

Outcome measures

Outcome measures
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=33 Participants CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Number of Participants That Achieved Engraftment	31 Participants

SECONDARY outcome

Timeframe: 2 years

To evaluate the effects of donor lymphocyte infusion (DLI) and cyclosporine A (CSA) withdrawal on tumor regression in participants who show progressive disease off of CSA and in the absence of grade \> II GVHD, or who are at risk for graft failure due to incomplete donor T-cell engraftment will receive one or more DLI. Tumor response assessed as follows: Complete response (CR): disappearance of signs \& symptoms of metastatic disease at least one month. Partial response (PR): a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting at least one month. No new metastatic lesions may appear. Stable disease (SD): tumor measurements not meeting the criteria of CR, PR, or PD. Progressive disease (PD): increase of 25% or greater in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or development of new metastatic disease.

Outcome measures

Outcome measures
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=42 Participants CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Number of Participants Who Received Donor Lymphocyte Infusion to Achieve Tumor Regression or Prevent Graft Failure	16 Participants

SECONDARY outcome

Timeframe: Day 100

Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD. Grades are defined as: Grade I: Skin = Maculopapular rash\< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day. Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day. Grade III: Skin = Rash on \>50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea \> 1500 mL/day. Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin \>15 mg/dL; Lower GI = Severe abdominal pain with or without ileus. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Outcome measures
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=42 Participants CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Number of Participants Who Developed Acute GVHD Grade 2 and Higher Grade II	9 Participants
Number of Participants Who Developed Acute GVHD Grade 2 and Higher Grade III-IV	11 Participants
Number of Participants Who Developed Acute GVHD Grade 2 and Higher No Acute GVHD	22 Participants

SECONDARY outcome

Timeframe: Day 100 to year 2

Population: 1 participant passed away prior to day 100 therefore is not evaluable.

Number of participants who developed Chronic Graft vs Host Disease (GVHD). Chronic GVHD is defined as symptoms that persist or appear after 100 days since the time of stem cell transplantation.

Outcome measures

Outcome measures
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=41 Participants CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Number of Participants Who Developed Chronic GVHD	18 Participants

Adverse Events

Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors

Serious events: 21 serious events

Other events: 7 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=42 participants at risk CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Gastrointestinal disorders Mucositis with fever	4.8% 2/42 • Number of events 2 • 8.5 years
Infections and infestations Pseudomonas sepsis	2.4% 1/42 • Number of events 1 • 8.5 years
Infections and infestations Parainfluenza pneumonia and septic shock	2.4% 1/42 • Number of events 1 • 8.5 years
Infections and infestations Pulmonary aspergillus	2.4% 1/42 • Number of events 1 • 8.5 years
Respiratory, thoracic and mediastinal disorders Dyspnea with progressive mets to lungs	2.4% 1/42 • Number of events 1 • 8.5 years
Gastrointestinal disorders Fecal impaction	2.4% 1/42 • Number of events 1 • 8.5 years
Infections and infestations Community acquired pneumonia	2.4% 1/42 • Number of events 1 • 8.5 years
Infections and infestations Pneumonia	2.4% 1/42 • Number of events 1 • 8.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive disease	28.6% 12/42 • Number of events 12 • 8.5 years
Gastrointestinal disorders Acute Graft VS Host Disease of GI Tract	9.5% 4/42 • Number of events 4 • 8.5 years
Gastrointestinal disorders Cytomegalovirus colitis	2.4% 1/42 • Number of events 2 • 8.5 years
Infections and infestations Invasive fungal infection	2.4% 1/42 • Number of events 1 • 8.5 years
Renal and urinary disorders Acute nephrotoxicity	2.4% 1/42 • Number of events 2 • 8.5 years
Infections and infestations Acute Respiratory Distress	2.4% 1/42 • Number of events 1 • 8.5 years
Hepatobiliary disorders Liver Failure	2.4% 1/42 • Number of events 1 • 8.5 years

Other adverse events

Other adverse events
Measure	Stem Cell Transplantation in Patients With Progressive and Incurable Metastatic Solid Tumors n=42 participants at risk CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given methotrexate: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given cyclosporin: CSA beginning day -4 and intravenous MTX on days +1, +3, and +6 will be given
Renal and urinary disorders Hemorrhagic cystitis	9.5% 4/42 • 8.5 years
Infections and infestations Cytomegalovirus disease	7.1% 3/42 • 8.5 years

Additional Information

Richard Childs, M.D. Principal Investigator, NIH, NHLBI

National Heart Lung and Blood Institute (NHLBI)

Phone: 301.451.7128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place