IGF-MTX Conjugate in the Treatment of Myelodysplastic Syndrome

NCT03175978 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AML-03
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this study is to determine the safety and tolerability of utilizing the insulin-like growth factor-1-methotrexate conjugate, 765IGF-MTX for the treatment of advanced, previously treated myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and oligoblastic acute myelogenous leukemia (oligoblastic AML or O-AML), including determining the maximum tolerated dose (MTD).

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, With Excess of Blasts

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events

  Number of Participants with Treatment-Emergent Adverse Events through study completion, up to a maximum duration of 10 28-day cycles.

  Up to 6 28-day cycles for one participant, and up to 10 28-day cycles for the other participant.

Secondary Outcomes (11)

• Response Criteria for AML, Complete Remission (CR)

  Assessed after 2 cycles of 28 days each.

• Response Criteria for AML, CR With Incomplete Recovery

  Assessed after 2 cycles of 28 days each.

• Response Criteria for AML, Relapse.

  Assessed after 6 cycles of 28 days each.

• Response Criteria for MDS, Complete Remission (CR)

  Assessed after 6 cycles of 28 days each.

• Response Criteria for MDS, Marrow CR

  Assessed after 2 cycles of 28 days each.

Study Arms (1)

IGF/MTX

EXPERIMENTAL

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.

Drug: IGF/MTX

Interventions

IGF/MTX DRUG

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

Also known as: insulin-like growth factor-1/methotrexate conjugate, 765IGF-methotrexate

IGF/MTX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of O-AML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy); or Diagnosis of MDS/CMML that is refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy (at least one line of therapy)
• Confirmed histologic diagnosis on bone marrow biopsy and aspirate within 28 days of trial entry prior to starting cycle 1.
• Platelets \> 10 x 10\^9/L
• ECOG performance status of 0, 1 or 2
• Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; prior use of systemic methotrexate \> 1 month prior to study entry is allowed. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion.
• Patient must have recovered from the acute toxic effects (≤ grade 1 CTCAE v.4.0) of previous anti-cancer treatment prior to study enrollment; the only exception is that grade 2 neuropathy is permitted
• Adequate organ function within 14 days of study registration
• Negative serum pregnancy test in females. Male and female patients with reproductive potential must use an approved contraceptive method if appropriate

You may not qualify if:

• ECOG PS \>2.
• Patients with active extramedullary disease.
• Pleural effusions or ascites.
• Grade 3 peripheral neuropathy within 14 days before enrollment.
• Active uncontrolled infection or severe systemic infection (enrollment is possible after control of infection).
• Myocardial infarction within ONE months prior to enrollment or has New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Pregnant or breastfeeding - methotrexate is Pregnancy Category X - has been reported to cause fetal death and/or congenital abnormalities. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 10% in patients with a prior history of diabetes, prior to study enrollment.
• Serious concomitant systemic disorders (e.g., active uncontrolled infection or uncontrolled diabetes) or psychiatric disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
• Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
• Any history of epilepsy or a seizure disorder or any known prior seizures.
• Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IGF or methotrexate.

Sponsors & Collaborators

• IGF Oncology, LLC: lead

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Regions Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Anemia, Refractory, with Excess of Blasts

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia

Results Point of Contact

• Title: Hugh McTavish
• Organization: IGF Oncology, LLC

hmctavish@igfoncology.com

651-207-8270

Study Officials

• Mrinal S Patniak

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2017
• First Posted: June 5, 2017
• Study Start: February 21, 2018
• Primary Completion: June 30, 2021
• Study Completion: September 30, 2021
• Last Updated: May 21, 2024
• Results First Posted: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)