Trial Outcomes & Findings for IGF-MTX Conjugate in the Treatment of Myelodysplastic Syndrome (NCT NCT03175978)
NCT ID: NCT03175978
Last Updated: 2024-05-21
Results Overview
Number of Participants with Treatment-Emergent Adverse Events through study completion, up to a maximum duration of 10 28-day cycles.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
2 participants
Primary outcome timeframe
Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.
Results posted on
2024-05-21
Participant Flow
Participant milestones
| Measure |
IGF/MTX
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Overall Study
STARTED
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2
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Overall Study
COMPLETED
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2
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=2 Participants
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=2 Participants
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Age, Categorical
>=65 years
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2 Participants
n=2 Participants
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Sex: Female, Male
Female
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0 Participants
n=2 Participants
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Sex: Female, Male
Male
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2 Participants
n=2 Participants
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Region of Enrollment
United States
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2 participants
n=2 Participants
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PRIMARY outcome
Timeframe: Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.Number of Participants with Treatment-Emergent Adverse Events through study completion, up to a maximum duration of 10 28-day cycles.
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Number of Participants With Treatment-Emergent Adverse Events
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2 Participants
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SECONDARY outcome
Timeframe: Assessed after 2 cycles of 28 days each.Population: One of the two patients had oligoblastic AML in addition to MDS. Only that one patient is included in this analysis.
Bone marrow blasts, platelet count, independence of red cell transfusions. Bone marrow blasts \<5%, absence of blasts with Auer rods, absence of extramedullyary disease, absolute neutrophil count \>1.0 x 10(9)/L, independence of red cell transfusions.
Outcome measures
| Measure |
IGF/MTX
n=1 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for AML, Complete Remission (CR)
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0 Participants
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SECONDARY outcome
Timeframe: Assessed after 2 cycles of 28 days each.Population: One of the two patients had Oligoblastic AML in addition to MDS. Only that patient is included in the analysis.
All CR criteria except for residual neutropenia (\<10(9)/L) or thrombocytopenia (\<100x 10(9)/L).
Outcome measures
| Measure |
IGF/MTX
n=1 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for AML, CR With Incomplete Recovery
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1 Participants
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SECONDARY outcome
Timeframe: Assessed after 6 cycles of 28 days each.Population: The one patient analyzed achieved complete remission after 2 cycles and relapse after 6 cycles.
Bone marrow blasts greater the 5% or reappearance of blasts in the blood, or development of extramedullary disease after complete remission or complete remission with incomplete recovery..
Outcome measures
| Measure |
IGF/MTX
n=1 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for AML, Relapse.
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1 Participants
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SECONDARY outcome
Timeframe: Assessed after 6 cycles of 28 days each.Bone marrow less than 5% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Peripheral blood values of Hgb greater than or equal to 11 d/dL, platelets greater than or equal to 100\*10\^9 platelets/L, neutrophils greater than or equal to 1.0\*10\^9 neutrophils/L, blasts equal to 0%.
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Complete Remission (CR)
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0 Participants
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SECONDARY outcome
Timeframe: Assessed after 2 cycles of 28 days each.Bone marrow less than or equal to 5% myeloblasts and decreased by greater than 50% over pretreatment.
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Marrow CR
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1 Participants
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SECONDARY outcome
Timeframe: Assessed after 6 cycles of 28 days each. Both patients had at least stable disease for at least 6 cycles.Failure to achieve at least PR, but no evidence of progression for greater than 8 weeks
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Stable Disease
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2 Participants
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SECONDARY outcome
Timeframe: Assessed after 6 cycles of 28 days each.Population: Neither patient met the criteria of failure at any time point (after 2, 4, and 6 cycles of 28 days each).
Death during treatment or disease progression characterized by worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Failure
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0 Participants
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SECONDARY outcome
Timeframe: Assessed after 2 cycles of 28 days each.Population: 2 subjects overall are analyzed, one subject is analyzed per row of data.
Absolute blast count.
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Disease Progression, Blasts Measurements
Subject 101 baseline, 1 participant per row
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22 percentage of bone marrow blasts
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Response Criteria for MDS, Disease Progression, Blasts Measurements
Subject 101, 8 weeks, 1 participant per row
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5 percentage of bone marrow blasts
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Response Criteria for MDS, Disease Progression, Blasts Measurements
Subject 102 baseline, 1 participant per row
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17 percentage of bone marrow blasts
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Response Criteria for MDS, Disease Progression, Blasts Measurements
Subject 102, 8 weeks, 1 partipant per row
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17 percentage of bone marrow blasts
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SECONDARY outcome
Timeframe: Assessed after 2 cycles of 28 days each.Population: 2 subjects are analyzed overall, but one subject is analyzed per row of data.
Hemoglobin in g/dL
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Disease Progression, Hgb
Subject 101, baseline, 1 participant per row
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7.3 g/dl
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Response Criteria for MDS, Disease Progression, Hgb
Subject 101, 8 weeks, 1 participant per row
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8.9 g/dl
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Response Criteria for MDS, Disease Progression, Hgb
Subject 102, baseline, 1 participant per row
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9.7 g/dl
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Response Criteria for MDS, Disease Progression, Hgb
Subject 102, 8 weeks, 1 participant per row
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9.9 g/dl
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SECONDARY outcome
Timeframe: Assessed after 2 cycles of 28 days each.Population: 2 subjects are analyzed overall, but one subject is analyzed per row of data.
Neutrophil count in 10(9)/L
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Disease Progression, Neutrophils
Subject 101, baseline, 1 participant per row
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0.04 neutrophils x10(9) per liter
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Response Criteria for MDS, Disease Progression, Neutrophils
Subject 101, 8 weeks, 1 participant per row
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0.75 neutrophils x10(9) per liter
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Response Criteria for MDS, Disease Progression, Neutrophils
Subject 102, 8 weeks, 1 participant per row
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1.29 neutrophils x10(9) per liter
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Response Criteria for MDS, Disease Progression, Neutrophils
Subject 102, baseline, 1 participant per row
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0.38 neutrophils x10(9) per liter
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SECONDARY outcome
Timeframe: All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.Population: Number of participants who survived for 23 months.
Survival over the full study time period and follow up to 23 months after initiating treatment.
Outcome measures
| Measure |
IGF/MTX
n=2 Participants
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Response Criteria for MDS, Survival, Death
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2 Participants
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Adverse Events
IGF/MTX
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IGF/MTX
n=2 participants at risk
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Skin and subcutaneous tissue disorders
Subcutaneous abscess
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50.0%
1/2 • Number of events 1 • All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
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Nervous system disorders
Syncope
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50.0%
1/2 • Number of events 1 • All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
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Other adverse events
| Measure |
IGF/MTX
n=2 participants at risk
This arm will evaluate use of IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated MDS, CMML and O-AML. 765IGF-MTX at a dose of 0.20 to 2.5 µequivalents per kg is administered as an IV infusion over 1.5 hours on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, as assessed after 2 cycles, unacceptable toxicity, or patient refusal.
IGF/MTX: 765IGF-MTX is supplied as a 5 ml sterile solution at 4.0 µeq per ml 765IGF-MTX concentration in aqueous 10 mM HCl in a 10 ml glass vial
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|---|---|
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Blood and lymphatic system disorders
Lymphocyte count decreased
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50.0%
1/2 • Number of events 1 • All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
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Blood and lymphatic system disorders
Worsening anemia
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50.0%
1/2 • Number of events 1 • All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
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Nervous system disorders
Peripheral motor neuropathy
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50.0%
1/2 • Number of events 1 • All-cause mortality was assessed up to 23 months, and serious and Other (Not Including Serious) Adverse Events were assessed for up to 22 months.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place