Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat B-cell Acute Lymphoblastic Leukemia(B-ALL)
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MOR00208 (formerly Xmab5574) intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody |
Drug: MOR00208 (formerly Xmab5574)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
- 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 treatment-emergent AEs
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ohio State University Medical Center | Columbus | Ohio | United States | 43201 |
| 2 | St. Jude Children's Research Hospital | Memphis | Tennessee | United States | 38105 |
| 3 | University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- MorphoSys AG
Investigators
- Principal Investigator: Elias Jabbour, MD, MDA
- Principal Investigator: Rebecca Klisovic, MD, Ohio State University
- Principal Investigator: Wing H. Leung, M.D., PhD, St. Jude Children's Research Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MOR208C202
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Period Title: Overall Study | |
| STARTED | 22 |
| COMPLETED | 6 |
| NOT COMPLETED | 16 |
Baseline Characteristics
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) |
| Overall Participants | 22 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
46.82
(17.098)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
10
45.5%
|
| Male |
12
54.5%
|
| Body Mass Index (kg/m2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg/m2] |
29
(8.496)
|
Outcome Measures
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR= CR (Complete Remission) + PR (Partial Remission) Antitumor activity of MOR00208 |
| Time Frame | Throughout during study until progression, after each treatment cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Measure Participants | 22 |
| Number [participants] |
2
9.1%
|
| Title | Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Measure Participants | 22 |
| Responder 1 |
56
|
| Responder 2 |
28
|
| Title | Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam |
|---|---|
| Description | Number of patients with at least one treatment-emergent AE |
| Time Frame | weekly, up to 7 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Measure Participants | 22 |
| Number [patients] |
22
|
| Title | Pharmacokinetics of MOR00208 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Measure Participants | 22 |
| Mean (Standard Deviation) [mcg/mL] |
198
(63.5)
|
| Title | Number of Patients Who Develop Ant-MOR00208 Antibodies as a Measure of Immunogenicity |
|---|---|
| Description | |
| Time Frame | monthly, up to 7 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Anti-MOR208 antibodies were not observed in any patients treated during this study. |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Measure Participants | 22 |
| Number [patients] |
0
|
| Title | Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam |
|---|---|
| Description | Number of patients with treatment-emergent AEs |
| Time Frame | weekly, up to 7 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) |
|---|---|
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 |
| Measure Participants | 22 |
| Number [number of patients with 1 or more AE] |
22
|
Adverse Events
| Time Frame | From signature of informed consent till up to 30 days after last study drug administration, or longer, as necessary. | |
|---|---|---|
| Adverse Event Reporting Description | Treatment-related Adverse Events | |
| Arm/Group Title | MOR00208 (Formerly Xmab5574) | |
| Arm/Group Description | intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody MOR00208 (formerly Xmab5574) Total Patients Screened: 30 Total patients Enrolled (at least one infusion with study treatment): 22 | |
All Cause Mortality |
||
| MOR00208 (Formerly Xmab5574) | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/22 (22.7%) | |
Serious Adverse Events |
||
| MOR00208 (Formerly Xmab5574) | ||
| Affected / at Risk (%) | # Events | |
| Total | 17/22 (77.3%) | |
| Blood and lymphatic system disorders | ||
| Febrile Neutropenia | 4/22 (18.2%) | |
| Gastrointestinal disorders | ||
| Diarrhoea | 2/22 (9.1%) | |
| General disorders | ||
| Disease Progression | 6/22 (27.3%) | |
| Pyrexia | 5/22 (22.7%) | |
| Tumor lysis syndrome | 2/22 (9.1%) | |
| Infections and infestations | ||
| Sepsis | 3/22 (13.6%) | |
Other (Not Including Serious) Adverse Events |
||
| MOR00208 (Formerly Xmab5574) | ||
| Affected / at Risk (%) | # Events | |
| Total | 22/22 (100%) | |
| Blood and lymphatic system disorders | ||
| Neutrophil count decreased | 4/22 (18.2%) | |
| Anaemia | 4/22 (18.2%) | |
| Platelet count decreased | 4/22 (18.2%) | |
| White blood cell count decreased | 2/22 (9.1%) | |
| Thrombocytopenia | 2/22 (9.1%) | |
| Lymphopenia | 1/22 (4.5%) | |
| Febrile neutropenia | 1/22 (4.5%) | |
| Neutropenia | 1/22 (4.5%) | |
| Cardiac disorders | ||
| Hypertension | 4/22 (18.2%) | |
| Sinus tachycardia | 2/22 (9.1%) | |
| Bradycardia | 1/22 (4.5%) | |
| Supraventricular tachycardia | 1/22 (4.5%) | |
| Eye disorders | ||
| Ocular hyperaemia | 1/22 (4.5%) | |
| Vision blurred | 1/22 (4.5%) | |
| Strabismus | 1/22 (4.5%) | |
| Gastrointestinal disorders | ||
| Constipation | 6/22 (27.3%) | |
| Diarrhoea | 4/22 (18.2%) | |
| Gastrooesophageal reflux disease | 3/22 (13.6%) | |
| Vomiting | 2/22 (9.1%) | |
| Proctalgia | 1/22 (4.5%) | |
| Decreased appetite | 1/22 (4.5%) | |
| Haemorrhoids | 1/22 (4.5%) | |
| Lower gastrointestinal haemorrhage | 1/22 (4.5%) | |
| Dyspepsia | 1/22 (4.5%) | |
| Oropharyngeal pain | 1/22 (4.5%) | |
| Gingival pain | 1/22 (4.5%) | |
| Periodontal disease | 1/22 (4.5%) | |
| Pharyngitis | 1/22 (4.5%) | |
| Lip disorder | 1/22 (4.5%) | |
| General disorders | ||
| Infusion related reaction | 13/22 (59.1%) | |
| Fatigue | 9/22 (40.9%) | |
| Nausea | 6/22 (27.3%) | |
| Abdominal pain | 4/22 (18.2%) | |
| Pyrexia | 4/22 (18.2%) | |
| Epistaxis | 3/22 (13.6%) | |
| Chills | 3/22 (13.6%) | |
| Oedema peripheral | 3/22 (13.6%) | |
| Confusional state | 3/22 (13.6%) | |
| Oedema | 3/22 (13.6%) | |
| Agitation | 2/22 (9.1%) | |
| Presyncope | 2/22 (9.1%) | |
| Mucosal inflammation | 2/22 (9.1%) | |
| Oral pain | 1/22 (4.5%) | |
| Chest discomfort | 1/22 (4.5%) | |
| Lymphoedema | 1/22 (4.5%) | |
| Myalgia | 1/22 (4.5%) | |
| Tremor | 1/22 (4.5%) | |
| Abdominal distension | 1/22 (4.5%) | |
| Dysgeusia | 1/22 (4.5%) | |
| Flushing | 1/22 (4.5%) | |
| Dysphonia | 1/22 (4.5%) | |
| Hyperhidrosis | 1/22 (4.5%) | |
| Weight increased | 1/22 (4.5%) | |
| Malaise | 1/22 (4.5%) | |
| Migraine | 1/22 (4.5%) | |
| Lymph node pain | 1/22 (4.5%) | |
| Tumour lysis syndrome | 1/22 (4.5%) | |
| Weight decreased | 1/22 (4.5%) | |
| Swelling face | 1/22 (4.5%) | |
| Lethargy | 1/22 (4.5%) | |
| Pain in extremity | 1/22 (4.5%) | |
| Asthenia | 1/22 (4.5%) | |
| Allergic transfusion reaction | 1/22 (4.5%) | |
| Leukaemic infiltration | 1/22 (4.5%) | |
| Hepatobiliary disorders | ||
| Aspartate aminotransferase increased | 5/22 (22.7%) | |
| Alanine aminotransferase increased | 4/22 (18.2%) | |
| Gamma-glutamyltransferase increased | 4/22 (18.2%) | |
| Hepatorenal syndrome | 1/22 (4.5%) | |
| Immune system disorders | ||
| Graft versus host disease | 1/22 (4.5%) | |
| Infections and infestations | ||
| Cytomegalovirus viraemia | 1/22 (4.5%) | |
| Hepatitis viral | 1/22 (4.5%) | |
| Sepsis | 1/22 (4.5%) | |
| Urinary tract infection | 1/22 (4.5%) | |
| Device related infection | 1/22 (4.5%) | |
| Lung infection | 1/22 (4.5%) | |
| Infection | 1/22 (4.5%) | |
| Wound infection | 1/22 (4.5%) | |
| Alpha haemolytic streptococcal infection | 1/22 (4.5%) | |
| Corynebacterium infection | 1/22 (4.5%) | |
| Injury, poisoning and procedural complications | ||
| Contusion | 3/22 (13.6%) | |
| Subdural haematoma | 1/22 (4.5%) | |
| Fall | 1/22 (4.5%) | |
| Investigations | ||
| Blood albumin decreased | 1/22 (4.5%) | |
| Blood amylase increased | 1/22 (4.5%) | |
| International normalised ratio increased | 1/22 (4.5%) | |
| Blood alkaline phosphatase increased | 1/22 (4.5%) | |
| Hypoalbuminaemia | 1/22 (4.5%) | |
| Metabolism and nutrition disorders | ||
| Hypokalaemia | 6/22 (27.3%) | |
| Hyperglycaemia | 6/22 (27.3%) | |
| Hyperkalaemia | 5/22 (22.7%) | |
| Hypocalcaemia | 4/22 (18.2%) | |
| Hypomagnesaemia | 4/22 (18.2%) | |
| Blood glucose increased | 1/22 (4.5%) | |
| Blood magnesium decreased | 1/22 (4.5%) | |
| Acidosis | 1/22 (4.5%) | |
| Hypoglycaemia | 1/22 (4.5%) | |
| Hyponatraemia | 1/22 (4.5%) | |
| Hypophosphataemia | 1/22 (4.5%) | |
| Hyperphosphataemia | 1/22 (4.5%) | |
| Metabolic acidosis | 1/22 (4.5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Muscular weakness | 3/22 (13.6%) | |
| Joint range of motion decreased | 1/22 (4.5%) | |
| Bone pain | 1/22 (4.5%) | |
| Back pain | 1/22 (4.5%) | |
| Nervous system disorders | ||
| Paraesthesia | 3/22 (13.6%) | |
| Headache | 3/22 (13.6%) | |
| Dizziness | 2/22 (9.1%) | |
| Brachial plexopathy | 1/22 (4.5%) | |
| Syncope | 1/22 (4.5%) | |
| Trigeminal nerve disorder | 1/22 (4.5%) | |
| Encephalopathy | 1/22 (4.5%) | |
| Dyskinesia | 1/22 (4.5%) | |
| Intracranial pressure increased | 1/22 (4.5%) | |
| Psychiatric disorders | ||
| Insomnia | 2/22 (9.1%) | |
| Anxiety | 2/22 (9.1%) | |
| Depression | 1/22 (4.5%) | |
| Renal and urinary disorders | ||
| Blood creatinine increased | 2/22 (9.1%) | |
| Pollakiuria | 2/22 (9.1%) | |
| Renal failure acute | 2/22 (9.1%) | |
| Renal failure | 2/22 (9.1%) | |
| Hyperuricaemia | 2/22 (9.1%) | |
| Haematuria | 1/22 (4.5%) | |
| Cystitis | 1/22 (4.5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Dyspnoea | 5/22 (22.7%) | |
| Cough | 4/22 (18.2%) | |
| Upper-airway cough syndrome | 2/22 (9.1%) | |
| Pleural effusion | 2/22 (9.1%) | |
| Pleuritic pain | 1/22 (4.5%) | |
| Productive cough | 1/22 (4.5%) | |
| Atelectasis | 1/22 (4.5%) | |
| Hypoxia | 1/22 (4.5%) | |
| Sinusitis | 1/22 (4.5%) | |
| Dyspnoea exertional | 1/22 (4.5%) | |
| Nasal congestion | 1/22 (4.5%) | |
| Pneumonia | 1/22 (4.5%) | |
| Chest pain | 1/22 (4.5%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash maculo-papular | 1/22 (4.5%) | |
| Rash erythematous | 1/22 (4.5%) | |
| Vascular disorders | ||
| Hypotension | 2/22 (9.1%) | |
| Petechiae | 1/22 (4.5%) | |
| Haemangioma of liver | 1/22 (4.5%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
As specified in the respective clinical trial agreements with the PI.
Results Point of Contact
| Name/Title | Dr. Sumeet Ambarkhane, Director, Clinical Program Leader |
|---|---|
| Organization | MorphoSys AG |
| Phone | 004989899270 |
| sumeet.ambarkhane@morphosys.com |
- MOR208C202