Acute Lymphoblastic Leukemia
Conditions
Keywords
B-ALL, CD19, MOR208, MOR00208, Xmab5574, B-cell acute lymphoblastic leukemia, Fc-optimized Anti-CD19 Antibody
Brief summary
This is an open-label, multicentre study to characterize the safety and preliminary efficacy of the human anti CD19 antibody MOR00208 in adult subjects with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL)
Interventions
DRUGMOR00208 (formerly Xmab5574)
Sponsors
MorphoSys AG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with previously treated Philadelphia-chromosome-negative B-ALL, with progression after at least one prior therapy. Patients with Philadelphia-chromosome-positive B-ALL can only be included if they are refractory or intolerant to at least one tyrosine-kinase-inhibitor. * Male or female patients at least 16 years of age; if the patient is less than 18 years of age, the patient must have the ability to understand and give written assent in addition to the parent's/guardian's written informed consent. * Patients with histologically confirmed diagnosis of B-ALL * Mixed phenotype acute leukemia patients who have B cell immunophenotype. * Patients with an Eastern Cooperative Oncology Group performance status of less than or equal to 2 * Patients with a total bilirubin of less than or equal to 2.0 mg/dL * Patients with alanine aminotransferase or aspartate aminotransferase less than or equal to 2.5 times the upper limit of normal * Patients with a creatinine level of less than or equal to 2.0 mg/dL * If a female of childbearing potential, confirmation of a negative pregnancy test before enrollment and use of double-barrier contraception, confirmation of a negative pregnancy test before enrollment and use of oral contraceptive plus barrier contraceptive, or confirmation of having undergone clinically documented total hysterectomy, oophorectomy, or tubal ligation * If a male, use of an effective barrier method of contraception during the study and for 3 months after the last dose if sexually active with a female of childbearing potential * Patients with the ability to understand and give written informed consent and to comply with the study protocol
Exclusion criteria
* Patients who received previous treatment with an anti-CD19 antibody or fragments * Receipt of anti-CD20 therapy no greater than 4 weeks before the first study dose * Patients having undergone prior allogeneic stem cell transplantation within 3 months or having active graft versus host disease * Patients with known hypersensitivity to any excipient contained in the drug formulation * Patients with a New York Heart Association Class III or IV * History of stroke or myocardial infarction within the last 6 months * Patients with a history of positive human immunodeficiency virus test result (ELISA or western blot) * Patients with positive hepatitis serology. Hepatitis B (HBV): Patients with positive serology for hepatitis B, defined as positive for hepatitis B surface antigen (HbsAg) or total anti-hepatitis B core antibody (anti-Hbc). Patients positive for anti- Hbc may be included if hepatitis B viral DNA is not detectable. Hepatitis C (HCV): Patients with positive hepatitis C serology (defined as positive for anti-hepatitis C virus antibody (anti-HCV) unless HCV-RNA is confirmed negative. * Patients with active viral, bacterial, or systemic fungal infection requiring active parenteral treatment * Patients who are receiving active treatment/chemotherapy for another primary malignancy or have received any treatment, including surgery, radiation, or chemotherapy, within the past 5 years (except ductal breast cancer in situ, for nonmelanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ) * Patients who are pregnant or breastfeeding * Patients with major surgery or radiation therapy within 4 weeks prior to first study dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Throughout during study until progression, after each treatment cycle | ORR= CR (Complete Remission) + PR (Partial Remission) Antitumor activity of MOR00208 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT | Throughout during study until progression, after each treatment cycle | Two patients had a response to treatment. For one of the two patients a progression was recorded, the other patient was censored due to an AE. Conse quently, the planned Kaplan-Meier analyses of response duration and time to hematological relapse could not be calculated. |
| Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam | weekly, up to 7 months | Number of patients with at least one treatment-emergent AE |
| Pharmacokinetics of MOR00208 | weekly, up to 16 weeks, based on samples taken Pre-dose (ie before infusion start) | Steady State Trough Plasma Concentration (Cpre-dose) at 9th dose (infusion) |
| Number of Patients Who Develop Ant-MOR00208 Antibodies as a Measure of Immunogenicity | monthly, up to 7 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MOR00208 (Formerly Xmab5574) intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody
MOR00208 (formerly Xmab5574) | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | MOR00208 (Formerly Xmab5574) |
|---|---|
| Age, Continuous | 46.82 years STANDARD_DEVIATION 17.098 |
| Body Mass Index | 29 kg/m2 STANDARD_DEVIATION 8.496 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 22 |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 17 / 22 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR= CR (Complete Remission) + PR (Partial Remission) Antitumor activity of MOR00208
Time frame: Throughout during study until progression, after each treatment cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOR00208 (Formerly Xmab5574) | Overall Response Rate (ORR) | 2 participants |
Secondary
Number of Patients Who Develop Ant-MOR00208 Antibodies as a Measure of Immunogenicity
Time frame: monthly, up to 7 months
Population: Anti-MOR208 antibodies were not observed in any patients treated during this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOR00208 (Formerly Xmab5574) | Number of Patients Who Develop Ant-MOR00208 Antibodies as a Measure of Immunogenicity | 0 patients |
Secondary
Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT
Two patients had a response to treatment. For one of the two patients a progression was recorded, the other patient was censored due to an AE. Conse quently, the planned Kaplan-Meier analyses of response duration and time to hematological relapse could not be calculated.
Time frame: Throughout during study until progression, after each treatment cycle
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MOR00208 (Formerly Xmab5574) | Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT | Responder 1 | 56 days |
| MOR00208 (Formerly Xmab5574) | Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT | Responder 2 | 28 days |
Secondary
Pharmacokinetics of MOR00208
Steady State Trough Plasma Concentration (Cpre-dose) at 9th dose (infusion)
Time frame: weekly, up to 16 weeks, based on samples taken Pre-dose (ie before infusion start)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOR00208 (Formerly Xmab5574) | Pharmacokinetics of MOR00208 | 198 mcg/mL | Standard Deviation 63.5 |
Secondary
Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam
Number of patients with at least one treatment-emergent AE
Time frame: weekly, up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOR00208 (Formerly Xmab5574) | Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam | 22 patients |
Secondary
Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam
Number of patients with treatment-emergent AEs
Time frame: weekly, up to 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOR00208 (Formerly Xmab5574) | Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam | 22 number of patients with 1 or more AE |