Study of Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia With Inotuzumab Ozogamicin (InO)

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase II Study of a Chemotherapy-Free Induction Regimen for Ph+ Acute Lymphoblastic Leukemia (ALL) Incorporating Inotuzumab Ozogamicin (InO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04747912
• Other study ID #: IRB20-1749
• Status: Recruiting
• Phase: Phase 2
• Start date: March 2, 2021
• Est. completion date: May 1, 2026

Study information

• Verified date: August 2023
• Source: University of Chicago
• Contact: Cancer Clinical Trials Office
• Phone: 1-855-702-8222
• Email: cancerclinicaltrials[@]bsd.uchicago.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study will add an anti-cancer drug (called inotuzumab ozogamicin also known as "InO") to treatment for participants with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Doctors leading this study hope to learn if adding InO to standard induction treatment for Ph+ ALL will lead to quicker, complete molecular remission (where the disease is not detectable even with very sensitive testing techniques). The purpose of this research is to gather information regarding the effectiveness of InO in newly-diagnosed Ph+ ALL patients that have not yet received treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: May 1, 2026
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must be a newly diagnosed and untreated patient with Ph+ B-cell Acute Lymphoblastic Leukemia and CD22 expression on =20% of blasts.

2. 18 years old or older.

3. Bone marrow involvement with =20% lymphoblasts and demonstration of BCR-ABL1 via fluorescence in situ hybridization (FISH) studies or PCR-based testing. Patients with >1000/mm3 lymphoblasts in the peripheral blood that cannot undergo bone marrow biopsy and aspiration due to clinical condition are also eligible.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

5. Adequate organ function as confirmed by clinical/medical record.

6. Patients must be at least 2 weeks from major surgery, radiation therapy, or participation in other investigational trials, and must have recovered from clinically significant toxicities related to these prior treatments.

7. Patients must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee/Institutional Review Board prior to starting any screening or study-specific procedures.

8. Females of childbearing potential will use effective contraception during treatment with InO and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during treatment with Inotuzumab Ozogamicin and for at least 5 months after the last dose. A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria): a. Have undergone hysterectomy or bilateral oophorectomy; or have medically confirmed ovarian failure; or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).

9. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Isolated extramedullary disease.

2. Burkitt's or mixed-lineage leukemia.

3. Active central nervous system (CNS) leukemia.

4. Any prior therapy for ALL except for limited treatment (= 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal therapy. Patients who are being treated with chronic steroids for other reasons (eg, asthma, autoimmune disorders) are eligible.

5. Current or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). HIV testing may need to be performed in accordance with local regulations or local practice. Patients with HIV but an undetectable viral load are eligible for enrollment

6. Major surgery within = 2 weeks before randomization.

7. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.

8. Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for =2 years or are not currently requiring treatment.

9. Uncontrolled cardiac disease.

10. QTcF > 500 msec (based on the average of 3 consecutive ECGs).

11. History of chronic liver disease (eg, cirrhosis) or suspected alcohol abuse.

12. History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS).

13. Evidence of uncontrolled current serious active infection including sepsis, bacteremia, fungemia, or patients with a recent history (within 4 months) of deep tissue infections such as fasciitis or osteomyelitis.

14. Medications known to predispose to Torsades de Pointes are prohibited throughout the treatment period of the study.

15. Pregnant females; breastfeeding females; males with female partners of reproductive potential and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 5 months after the last dose of investigational product if male and 8 months after the last dose of investigational product if female.

16. Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the trial.

17. Participation in other investigational studies during active treatment phase.

18. Other severe acute, chronic medical, psychiatric condition, 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 Study Lead Principal Investigator, would make the patient inappropriate for entry into this study.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Leukemia
• ph+ Acute Lymphoblastic Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Inotuzumab ozogamicin
Inotuzumab ozogamicin, sold under the brand name Besponsa, is an anti-cancer drug used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia.
• Dasatinib
Dasatinib is a prescription treatment for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML).
• Dexamethasone
Dexamethasone is a steroid that prevents the release of substances in the body that cause inflammation.
• Methotrexate
Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia.
• Vincristine
Vincristine, also known as leurocristine and marketed under the brand name Oncovin among others, is a chemotherapy medication used to treat various types of cancer such as acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's disease, neuroblastoma, and small cell lung cancer among others.
• Ponatinib
A drug used to treat chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. It is used in patients whose cancer has the T315I mutation or whose cancer cannot be treated with other tyrosine kinase inhibitors. It is also being studied in the treatment of other types of cancer. Ponatinib blocks BCR-ABL, which may help keep cancer cells from growing and may kill them.
• Methotrexate for Injection
Methotrexate is a chemotherapy drug that is used to treat certain types of cancer and leukemia. When given intrathecally, it prevents leukemia cells entering the cerebrospinal fluid (CSF) around the spine and brain. Intrathecal chemotherapy is administered during a procedure called a lumbar puncture or through an ommaya reservoir (shunt).

Procedure:
• Allogenic Stem Cell Transplantation
A procedure in which a patient receives healthy blood-forming cells (stem cells) from a donor to replace their own stem cells that have been destroyed by treatment with radiation or high doses of chemotherapy. In an allogeneic stem cell transplant, the healthy stem cells may come from the blood or bone marrow of a related donor who is not an identical twin of the patient or from an unrelated donor who is genetically similar to the patient. An allogeneic stem cell transplant is most often used to treat blood cancers, such as leukemia and lymphoma, and certain types of blood or immune system disorders.

Locations

Country	Name	City	State
United States	University of Chicago Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Enter Complete Clinical Remission at 60 Days as Defined by Criteria Set By The International Scale	Complete clinical remission (when there are no signs of the disease) with a major molecular remission at 60 days as defined by participants who have a low ratio (less than or equal to .01%) of BCR-ABL1gene in their blood, according to criteria set by the International Scale for p210 BCR-ABL1.	60 days
Secondary	Overall Survival	The length of time from when the participant first receives study treatment to their death (due to any cause) as assessed by the treating investigator. Participants will be followed for 12 weeks after the last dose of study drug, until any study treatment-related toxicities have stabilized, or until death.	36 months
Secondary	Duration of Response	The length of time from the first documented complete response (participant shows no signs of cancer) or partial response (participant shows fewer signs of cancer) to disease progression or death. Partial/complete response will be assessed by bone marrow biopsies and blood tests.	36 months
Secondary	Duration of Complete Response	The length of time from the first documented complete response (when participant shows no signs of cancer) to disease progression or death as assessed by the treating investigator.	36 months
Secondary	Progression Free Survival	The time from treatment administration to documented disease progression or death from any cause as assessed by the treating investigator.	36 months
Secondary	Disease Control Rate Based on Number of Participants Who Respond to Treatment After 3 Months	The disease control rate based on the number of participants who show a complete response, partial response or no changes in disease (stable disease) after 3 months as assessed by bone marrow biopsies and neutrophil/complete blood count tests.	36 months
Secondary	Number of Participants with Complete Molecular Remission at 180 Days	Number of participants with complete molecular remission at 180 days as defined by the absence of a detectable BCR-ABL1 gene, according to criteria set by the International Scale for p210 BCR-ABL1. Complete molecular remission at 180 days will be assessed among participants who do not undergo allogenic stem cell transplantation after treatment.	36 months
Secondary	Number of Participants With Documented Veno-Occlusive Disease After Treatment	The number of patients with documented veno-occlusive disease as assessed by treating investigator.	36 months