Inotuzumab Ozogamicin Post-Transplant For Acute Lymphocytic Leukemia

NCT03104491 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE1916
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 7

Brief Summary

This study has two phases, Phase I and Phase II. The main goal of the Phase I portion of this research study is to see what doses post-transplant inotuzumab ozogamicin can safely be given to subjects without having too many side effects. The Phase II portion of this study is to see what side effects are seen with medication after transplant. Inotuzumab ozogamicin is a combination of an antibody and chemotherapy which has been shown to have significant activity against relapsed/refractory acute lymphocytic leukemia (ALL). Inotuzumab ozogamicin is considered experimental in this study.

Conditions

Acute Lymphocytic Leukemia

Keywords

allogeneic hematopoietic stem cell transplantation; donor chimerism

Outcome Measures

Primary Outcomes (7)

• Phase I MTD

  Defined post hematopoietic stem cell transplantation MTD

  Up to 112 days (16 weeks)

• Phase I DLTs

  Frequency of DLTs during the first two cycles in ALL-participants

  Up to 112 days (16 weeks)

• Phase II Median DFS

  Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  At 3 months after initial treatment

• Phase II Median DFS

  Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  At 6 months after initial treatment

• Phase II Median DFS

  Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  At 9 months after initial treatment

• Phase II Median DFS

  Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  At 1 year after initial treatment

• Phase II Median DFS

  Efficacy as measured by phase II DFS at one year, estimated using Kaplan-Meier, reported as median and 2-sided 80% and 95% Confidence Interval (CI) DFS is defined as "Time from date of first dose to the date of disease progression (ie,objective progression, relapse from CR/CRi), or death due to any cause, whichever occurs first (including post-study treatment follow-up disease assessments)". Difference in time-to-event endpoints will be tested using a 1-sided log-rank test at a significance level of 0.10 In Phase II, the null hypothesis of H0: DFS at 1-year ≤ 55% versus the alternative hypothesis of Ha: DFS at 1-year ≥ 75% using 1-sided alpha of 10% will be tested

  Post first dose of inotuzumab ozogamicin

Secondary Outcomes (65)

• Phase I Median DFS

  At 3 months after initial treatment

• Phase I Median DFS

  At 6 months after initial treatment

• Phase I Median DFS

  At 9 months after initial treatment

• Phase I Median DFS

  At 1 year after initial treatment

• Phase I Median DFS

  Post first dose of inotuzumab ozogamicin on Day 1, Cycle 1, where cycle length is 28 days

Study Arms (1)

Inotuzumab Ozogamicin

EXPERIMENTAL

Phase I: A maximum of 4 cycles will be allowed and doses will be adjusted in 0.1mg/m2 increments using a dose escalation scale depending on tolerability. Total range of dose levels for participants is 0.1-0.6mg/m\^2. Phase II: Participants will be enrolled until all Phase I participants have been followed and assessed for toxicity for at least 4 weeks after the fourth treatment dose of inotuzumab ozogamicin or 4 weeks after the participant goes off treatment, whichever comes first. Doses to be administered will be determined in the phase I portion of the study. The recommended phase 2 dose is 0.3mg/m2. Repeat cycles every 28 days for up to 4 cycles

Drug: Inotuzumab Ozogamicin

Interventions

Inotuzumab Ozogamicin DRUG

Inotuzumab ozogamicin, IV, 28 day cycles Phase 1 dosages: Dose Level -2 (0.1 mg/m\^2) Dose Level -1 (0.2 mg/m\^2) Dose Level 0 (0.3 mg/m\^2) Dose Level 1 (0.4 mg/m\^2) Dose Level 2 (0.5 mg/m\^2) Dose Level 3 (0.6 mg/m\^2)

Inotuzumab Ozogamicin

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CD22-positive Acute Lymphoblastic Leukemia
• Patients who underwent an allogeneic hematopoietic stem cell transplantation from any donor source for acute lymphocytic leukemia
• Patients who are between T+40 and T+100 after allogeneic transplantation. Patients must receive their first dose of inotuzumab at or before T+100.
• Patients who have/are either:
• Transplanted in hematologic first complete remission with evidence of minimal residual disease within 45 days of allogeneic transplantation
• Pre- or Post-Transplant Minimal Residual Disease defined by:
• Any detectable ALL (by flow cytometry, cytogenetics, or PCR techniques) as per clinical indication.
• In second or third complete remission at the time of allogeneic transplantation
• Treated with reduced intensity regimens or non-myeloablative conditioning regimens
• Lymphoid blast crisis of CML
• Are relapsed or refractory to at least 1 line of chemotherapy
• Philadelphia-like ALL
• Patients who have evidence of donor chimerism after allogeneic transplantation.
• ECOG Performance status \< 2
• Participants must have ANC \> 1,000/µL for 3 days and platelet transfusion independence as defined as a platelet count \> 50,000/µL for 7 days.

You may not qualify if:

• Patients with clinical evidence of disease progression prior to enrollment
• Persistent prior treatment toxicities Grade 2 and above according to NCI CTCAE Version 4.03 (with the exception for alopecia, neuropathy, etc.)
• Patients with inadequate organ function as defined by:
• Creatinine clearance \< 30ml/min
• Bilirubin \> 2X institutional upper limit of normal
• AST (SGOT) \> 2X institutional upper limit of normal
• ALT (SGPT) \> 2X institutional upper limit of normal
• GVHD grade III or IV (for patients with a prior allogeneic transplant).
• Active acute or chronic GVHD of the liver (for patients with a prior allogeneic transplant)
• History of VOD
• Use of concomitant TKI or sirolimus
• Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast)
• Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because inotuzumab ozogamicin may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with inotuzumab ozogamicin, breastfeeding should be discontinued if the mother is treated with inotuzumab ozogamicin. These potential risks may also apply to other agents used in this study.
• Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)

Sponsors & Collaborators

• Leland Metheny: lead

Study Sites (7)

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68106, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

ACTIVE NOT RECRUITING

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

RECRUITING

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

ACTIVE NOT RECRUITING

The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (1)

• Metheny LL, Sobecks R, Cho C, Fu P, Margevicius S, Wang J, Ciarrone L, Kopp S, Convents RD, Majhail N, Caimi PF, Otegbeye F, Cooper BW, Gallogly M, Malek E, Tomlinson B, Gerds AT, Hamilton B, Giralt S, Perales MA, de Lima M. A multicenter study of posttransplantation low-dose inotuzumab ozogamicin to prevent relapse of acute lymphoblastic leukemia. Blood Adv. 2024 Mar 26;8(6):1384-1391. doi: 10.1182/bloodadvances.2023011514.

  PMID: 38170741 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Inotuzumab Ozogamicin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Leland Metheny, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leland Metheny, MD

CONTACT

1-800-641-2422; CTUReferral@UHhospitals.org

Ron Sobecks, MD

CONTACT

216-444-6833; sobeckr@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: April 7, 2017
• Study Start: July 31, 2017
• Primary Completion: November 1, 2025
• Study Completion (Estimated): May 1, 2027
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

US (7)