Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Leukemia or Lymphoma Undergoing Stem Cell Transplantation

Lymphoma Clinical Trial

Official title:

Addition of Inotuzumab Ozogamicin Pre- and Post-Allogeneic Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03856216
• Other study ID #: 2018-0860
• Secondary ID: NCI-2019-0053120
• Status: Recruiting
• Phase: Phase 2
• Start date: October 28, 2019
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: M.D. Anderson Cancer Center
• Contact: Issa F Khouri
• Phone: 713-792-8750
• Email: ikhouri[@]mdanderson.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this phase II clinical study is to learn about the safety of inotuzumab ozogamicin when given with fludarabine, with or without bendamustine, melphalan, and rituximab before and after a stem cell transplant. Researchers also want to learn if inotuzumab ozogamicin when given after a stem cell transplant can help control leukemia and lymphoma. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug called ozogamicin. Inotuzumab attaches to CD22-positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving chemotherapy before a bone marrow or peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Sometimes the transplanted cells from a donor attack the body's normal cells (called graft-versus-host disease). Giving tacrolimus and filgrastim before or after the transplant may stop this from happening. Fludarabine, bendamustine, melphalan, and rituximab are commonly given before stem cell transplants. Giving inotuzumab ozogamicin with chemotherapy may work better in treating patients with leukemia or lymphoma undergoing stem cell transplantation.

Description:

PRIMARY OBJECTIVE:

I. To assess the safety of the addition of inotuzumab ozogamicin (IO) pre- and post-allogeneic transplantation in patients with CD22-positive hematological malignancies.

SECONDARY OBJECTIVES:

I. Overall survival, progression-free survival and relapse rates. II. Treatment-related mortality. III. Cumulative incidence of acute and chronic graft-versus-host disease (GVHD).

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I: Patients with acute lymphoblastic leukemia (ALL) and aggressive lymphoma receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, fludarabine IV over 1 hour on days -5 to -2, melphalan IV over 30 minutes on day -2, and tacrolimus IV continuously beginning on day -2 then orally (PO) once daily (QD) or twice daily (BID) for about 6 months. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients receive cylophosphamide IV over 3 hours and mesna IV on days +3 to +4 and filgrastim-sndz subcutaneously (SC) QD beginning 1 week after the transplant until blood cell levels return to normal.

GROUP II: Patients with indolent lymphoma receive inotuzumab ozogamicin IV over 1 hour on day -13, fludarabine IV over 1 hour and bendamustine IV over 30 minutes to 1 hour on days -5 to -3, and tacrolimus IV continuously beginning on day -2 then PO QD or BID for about 6 months. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients then receive rituximab IV over 4-6 hours on days 1 and 8, cyclophosphamide IC over 3 hours and mesna IV on days +3 to +4, and filgrastim-sndz SC once a day beginning 1 week after the transplant.

MAINTENANCE: Between 45 and 100 days after stem cell transplantation, all patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 2. Beginning 28 to 100 days after start of first cycle, patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: March 31, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 70 Years

Eligibility

Inclusion Criteria:

• Participants age 12 to 70.

• English and non-English speaking participants are eligible.

• CD22+ lymphoid malignancies including B-ALL

• Eligible to receive a reduced-intensity alloSCT

Participants with:

• Indolent lymphoma participants who failed conventional treatment; or,

• Acute lymphoblastic leukemia (ALL), aggressive lymphoma, indolent lymphoma in transformation, or those who have failed = three small molecule inhibitors

• Donor: HLA compatible related or matched unrelated donor (HLA-A, B, C, DRB1)

• Performance status of 0 to 2, Lansky = 80 for < 16 years and Karnofsky = 80 for = 16 years of age.

• Adequate organ function at time of study entry

1. Creatinine less than or equal to 1.6 mg/dL

2. Bilirubin less than 1.6 mg/dL

3. SGPT < 2 x UL

4. Ejection fraction >/= 40%

5. FEV1, FVC and cDLCO >/= 40%

• Negative Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

Exclusion Criteria:

• Human immunodeficiency virus (HIV) positive.

• Prior autologous transplant less than 1 year prior to consent.

• Active and uncontrolled disease/infection.

• Unable or unwilling to sign consent.

• Current active hepatic or biliary disease (with exception of Gilbert's syndrome).

• Active hepatitis B or C.

• Recent chemotherapy or radiation within 3 weeks of study entry. Standard biological agents such as rituximab, TKIs such as ibrutinib, and venetoclax are allowed to be given within 3 days prior to receiving inotuzumab ozogamicin.

• Prior inotuzumab ozogamicin within 3 weeks of study entry.

• Peripheral blast count of greater than 10 K/mL.

• QTcF interval > 470 ms.

• Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• B Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphocytic Neoplasm
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Procedure:
• Allogeneic Bone Marrow Transplantation
Given IV

Drug:
• Bendamustine
Given IV

Biological:
• Filgrastim-sndz
Given IV

Drug:
• Fludarabine
Given IV

Biological:
• Inotuzumab Ozogamicin
Given IV

Drug:
• Melphalan
Given IV

Procedure:
• Peripheral Blood Stem Cell Transplantation
Given IV

Biological:
• Rituximab
Given IV

Drug:
• Tacrolimus
Given IV and PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of grade 3 or higher renal, hepatic, cardiac, pulmonary, or neurologic toxicity	Will be assessed using the Bayesian method of Thall, Simon, and Estey. At the end of the trial, the rates of severe toxicity will be summarized, and analyses will be performed to assess the relationship between each toxicity endpoint and covariates of interest using logistic regression.	Up to 30 days after cycle 1 of maintenance therapy
Secondary	Treatment-related mortality (TRM)	The cumulative incidence of TRM will be assessed in a competing risks framework with the competing risk of disease relapse. Regression models will be fit to assess the relationship between each and covariates of interest using the method of Fine and Gray.	Up to 2 years
Secondary	Relapse		Up to 2 years
Secondary	Overall survival (OS)	The distribution of OS will be assessed using the Kaplan-Meier method, and distributions will be compared using the log-rank test. Cox proportional hazards regression models will be fit to assess the relationship between OS and covariates of interest.	Up to 2 years
Secondary	Progression-free survival (PFS)	The distribution of PFS will be assessed using the Kaplan-Meier method, and distributions will be compared using the log-rank test. Cox proportional hazards regression models will be fit to assess the relationship between PFS and covariates of interest.	Up to 2 years
Secondary	Acute graft versus host disease (GVHD)	The cumulative incidence of acute GvHD will be assessed in a competing risks framework with competing risks of death without relapse and disease relapse. The method of Fine and Gray will be used to assess the association between GvHD and covariates of interest.	Up to 2 years
Secondary	Chronic GVHD	The cumulative incidence of chronic GvHD will be assessed in a competing risks framework with competing risks of death without relapse and disease relapse. The method of Fine and Gray will be used to assess the association between GvHD and covariates of interest.	Up to 2 years

External Links

•   MD Anderson Cancer Center