Inotuzumab Ozogamicin in Treating Patients With Relapsed or Refractory CD22 Positive Acute Lymphoblastic Leukemia

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03094611
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 27.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well inotuzumab ozogamicin works in treating patients with CD22 positive acute lymphoblastic leukemia that has come back or does not respond to treatment. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.

Condition or Disease	Intervention/Treatment	Phase
CD22 Positive; Recurrent Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia	Biological: Inotuzumab Ozogamicin	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the objective response rate of low dose of inotuzumab ozogamicin as measured by the hematologic remission rate (complete remission [CR] + CR with incomplete platelet recovery [CRp] + CR with incomplete bone marrow recovery [CRi]) in patients in first, second or later salvage setting.

SECONDARY OBJECTIVES:

1. To evaluate the overall safety profile and the efficacy; the efficacy is measured by the hematologic response rate (CR + CRi + PR), durations of response (DoR) and remission (DoR1), progression free survival (PFS), and overall survival (OS).

OUTLINE:

Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Low Dose Inotuzumab Ozogamicin in Patients With Relapsed and Refractory CD22 Positive Acute Lymphocytic Leukemia
• Actual Study Start Date: Nov 30, 2017
• Actual Primary Completion Date: Mar 11, 2020
• Actual Study Completion Date: Mar 11, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (inotuzumab ozogamicin) Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles.

Biological: Inotuzumab Ozogamicin; Given IV; Other Names: Besponsa CMC-544 Way 207294 WAY-207294

Outcome Measures

Primary Outcome Measures

1. Number of Participants to Achieve Complete Remission (CR) [Up to 2 years]

   Complete Remission (CR) is the normalization of the peripheral blood and bone marrow with </= 5% blasts with a granulocyte count of 1X10^9/L or above and a platelet count of >/= 100X10^9/L and absence of extramedullary disease.

Secondary Outcome Measures

1. Participants With a Grade 3 or 4 Non-hematologic Adverse Event (AE) [Up to 2 years]

   For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.

2. Duration of Response [Up to 3 years]

   The date of Complete Response to the date of loss of response or last follow-up.

3. Progression Free Survival [Up to 3 years]

   Time from date of treatment start until the date of first objective documentation of disease-relapse.

4. Overall Survival [Up to 3 years]

   Time from date of treatment start until date of death due to any cause or last Follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients at least 12 years of age

• Patients with a diagnosis of CD22-positive acute lymphoblastic leukemia (ALL) based on local immunophenotyping and histopathology who have:

• Refractory disease, defined as disease progression or no response while receiving their most recent prior anti-cancer therapy,

• Relapsed disease, defined as response to their most recent prior anti-cancer therapy with subsequent relapse

• Performance status of 0 to 3

• Serum creatinine =< 2 x upper limit of normal (ULN) or estimated creatinine clearance

= 15 mL/min as calculated using the method standard for the institution

• Total serum bilirubin =< 1.5 x ULN unless the patient has documented Gilbert syndrome. If organ function abnormalities are considered due to tumor, total serum bilirubin must be =< 2 x ULN

• Aspartate and alanine aminotransferase (AST or ALT) =< 2.5 x ULN

• No active or co-existing malignancy requiring chemotherapy or radiation within 6 months

• Female subjects of childbearing potential should be willing to use effective methods birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Effective methods of birth control include birth control pills or injections, intrauterine devices (IUDs), or double-barrier methods (for example, a condom in combination with spermicide)

• Male subjects should agree to use an effective method of contraception starting with the first dose of study therapy through the duration of treatment

Exclusion Criteria:

• Pregnant or nursing women

• Known to be human immunodeficiency virus (HIV)+

• Philadelphia chromosome (Ph)+ ALL

• Active and uncontrolled disease/infection as judged by the treating physician

• Unable or unwilling to sign the consent form

• Prior allogeneic stem cell transplantation (ASCT) or other anti-CD22 immunotherapy within =< 4 months before first dose of study treatment

• Active central nervous system (CNS) or extramedullary disease unless approved by the principal investigator (PI)

• Monoclonal antibodies therapy within 2 weeks before study entry

• Radiotherapy and cancer chemotherapy (except for intrathecal chemotherapy, hydroxyurea, and cytarabine. Cytarabine and hydroxyurea are allowed to be used emergently in case of leukocytosis) or any investigational drug within 2 weeks before study entry

• Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 12, 2018

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT03094611
• Other Study ID Numbers: 2015-0870; NCI-2018-01237; 2015-0870; P30CA016672
• First Posted: Mar 29, 2017
• Last Update Posted: Apr 12, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Inotuzumab Ozogamicin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: January 2017 to January 2019

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Period Title: Overall Study
STARTED	4
COMPLETED	2
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 75%
>=65 years	1 25%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	46
Sex: Female, Male (Count of Participants)
Female	1 25%
Male	3 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 75%
More than one race	0 0%
Unknown or Not Reported	1 25%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants to Achieve Complete Remission (CR)
Description	Complete Remission (CR) is the normalization of the peripheral blood and bone marrow with </= 5% blasts with a granulocyte count of 1X10^9/L or above and a platelet count of >/= 100X10^9/L and absence of extramedullary disease.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Measure Participants	4
Count of Participants [Participants]	3 75%

2. Secondary Outcome

Title	Participants With a Grade 3 or 4 Non-hematologic Adverse Event (AE)
Description	For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Measure Participants	4
Count of Participants [Participants]	1 25%

3. Secondary Outcome

Title	Duration of Response
Description	The date of Complete Response to the date of loss of response or last follow-up.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Measure Participants	4
Median (Full Range) [Months]	17.0

4. Secondary Outcome

Title	Progression Free Survival
Description	Time from date of treatment start until the date of first objective documentation of disease-relapse.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Measure Participants	4
Median (Full Range) [Months]	11.7

5. Secondary Outcome

Title	Overall Survival
Description	Time from date of treatment start until date of death due to any cause or last Follow-up.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
Measure Participants	4
Median (Full Range) [Months]	19.6

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Treatment (Inotuzumab Ozogamicin)
Arm/Group Description	Patients receive inotuzumab ozogamicin IV over 1 hour on days 1, 8 and 15 of cycle 1 and on days 1 and 8 beginning cycle 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients whose disease gets worse after responding for 3 months, may be retreated for up to 6 additional cycles. Patients whose disease responds to treatment may receive up to 5 additional cycles. Inotuzumab Ozogamicin: Given IV
All Cause Mortality
	Treatment (Inotuzumab Ozogamicin)
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Serious Adverse Events
	Treatment (Inotuzumab Ozogamicin)
	Affected / at Risk (%)	# Events
Total	1/4 (25%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Inotuzumab Ozogamicin)
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Gastrointestinal disorders
Diarrhea	2/4 (50%)	2
Nausea	3/4 (75%)	3
Vomiting	1/4 (25%)	1
Abdominal Distension	1/4 (25%)	1
General disorders
Headache	2/4 (50%)	2
Fever	1/4 (25%)	1
Rash	1/4 (25%)	1
Investigations
Alkaline Phosphatase Increased	3/4 (75%)	3
Aspartate Aminotransferase Increased	3/4 (75%)	3
Hyperbilirubinemia	2/4 (50%)	3
Alanine Aminotransferase Increase	1/4 (25%)	1
Metabolism and nutrition disorders
Hypophosphatemia	1/4 (25%)	1
Hypokalemia	1/4 (25%)	1
Nervous system disorders
Dizziness	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.