Phase 2
N=136
A Clinical Study Using MEDI-551 in Adult Participants With Relapsed or Refractory Advanced B-Cell Malignancies
B-cell Malignancies · Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00983619 ↗Enrolled (actual)
136
Serious AEs
35.3%
Results posted
May 2020
Primary outcome: Primary: Optimal Biologic Dose of MEDI-551 for Part A — 12 mg/Kg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MEDI-551 (Drug); Rituximab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MedImmune LLC
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Optimal Biologic Dose of MEDI-551 for Part A |
12 | — |
| PRIMARY Highest Protocol-defined Dose for Part B |
24 | — |
| PRIMARY Highest Protocol-defined Dose for Part C |
12 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part A, Part B, and Part C |
3; 4; 3; 6; 3; 76 | — |
| PRIMARY Number of Participants With Dose Limiting Toxicities of MEDI-551 in Part A, Part B, and Part C |
0; 0; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part A, Part B, and Part C |
0; 2; 0; 0; 1; 6 | — |
| PRIMARY Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part A, Part B, and Part C |
1; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part A, Part B, and Part C |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Percentage of Participants With Complete Response for Part B, Part C, and Part D |
33.3; 0; 33.3; 18.8; 0 | — |
| PRIMARY Percentage of Participants With Partial Response for Part B, Part C, and Part D |
33.3; 33.3; 33.3; 25.0; 23.1 | — |
| PRIMARY Duration of Complete Response for Part B, Part C, and Part D |
NA; NA; NA | — |
| PRIMARY Percentage of Participants With Objective Response Rate for Part B, Part C, and Part D |
66.7; 33.3; 66.7; 43.8; 23.1 | — |
| PRIMARY Duration of Objective Response for Part B, Part C, and Part D |
NA; 27.5; 3.7; NA; 3.7 | — |
| PRIMARY Percentage of Participants With Disease Control Rate for Part B, Part C, and Part D |
100; 100; 100; 68.8; 46.2 | — |
| PRIMARY Duration of Disease Control for Part B, Part C, and Part D |
NA; 29.8; 5.5; 14.6; 3.8 | — |
| PRIMARY Time to Response for Part B, Part C, and Part D |
6.5; 12.0; 1.8; 2.0; 1.8 | — |
| PRIMARY Progression Free Survival for Part B, Part C, and Part D |
NA; 29.8; 5.5; 3.5; 2.0 | — |
| PRIMARY Overall Survival for Part B, Part C, and Part D |
NA; NA; 25.0; 33.4; 17.9 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) for Part D |
14; 5 | — |
| SECONDARY Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Part D |
2; 1; 3; 1; 4; 1 | — |
| SECONDARY Number of Participants With Abnormal Vital Signs Reported as TEAEs in Part D |
2; 1; 1; 1; 1; 2 | — |
| SECONDARY Number of Participants With Abnormal Electrocardiograms Reported as TEAEs in Part D |
1 | — |
| SECONDARY Percentage of Participants With Complete Response for Part A |
33.3; 0; 0; 20.0; 0; 12.5 | — |
| SECONDARY Percentage of Participants With Partial Response for Part A |
33.3; 0; 0; 0; 33.3; 15.3 | — |
| SECONDARY Duration of Complete Response for Part A |
7.1; 14.9; 14.3 | — |
| SECONDARY Percentage of Participants With Objective Response Rate for Part A |
66.7; 0; 0; 20.0; 33.3; 27.8 | — |
| SECONDARY Duration of Objective Response for Part A |
8.8; 15.0; 3.0; 19.8 | — |
| SECONDARY Percentage of Participants With Disease Control Rate for Part A |
66.7; 50.0; 66.7; 80.0; 66.7; 73.6 | — |
| SECONDARY Duration of Disease Control for Part A |
12.6; NA; NA; 10.9; 6.6; 18.0 | — |
| SECONDARY Time to Response for Part A |
3.7; 1.9; 3.6; 3.2 | — |
| SECONDARY Progression Free Survival for Part A |
12.6; 5.9; 3.5; 4.9; 6.6; 11.3 | — |
| SECONDARY Overall Survival for Part A |
NA; 44.6; 9.9; NA; 8.1; 45.3 | — |
| SECONDARY Trough Serum Concentration of MEDI-551 by Treatment Cycle |
NA; 0.333; NA; NA; NA; NA | — |
| SECONDARY Peak Serum Concentration of MEDI-551 by Treatment Cycle |
12.3; 22.8; 46.0; 100; 166; 280 | — |
| SECONDARY Area Under the Concentration Curve at Steady State (AUCss) of MEDI-551 |
212; 287; 479; 1660; 2880; 5720 | — |
| SECONDARY Apparent Clearance of MEDI-551 |
206; 302; 373; 210; 268; 198 | — |
| SECONDARY Volume of Distribution of MEDI-551 |
3970; 3920; 4350; 4070; 4210; 4230 | — |
| SECONDARY Terminal Half-life (t1/2) of MEDI-551 |
26.0; 17.3; 13.3; 22.1; 21.7; 27.9 | — |
| SECONDARY Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI-551 |
0; 1; 0; 0; 0; 2 | — |
| SECONDARY B-cell Concentration in Serum |
— | — |
| SECONDARY Immunoglobulin (Ig) Concentration in Serum |
120.00; 110.00; 81.00; 61.67; 93.33; 93.01 | — |
Summary
The purpose of this study is to determine the maximum tolerated dose of this drug (MEDI-551) in participants with advanced B-cell malignancies. Expansion to occur at maximum tolerated dose (MTD), or if not reached, at optimal biologic dose (OBD).
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed CLL, DLBCL, FL, or MM;
- Karnofsky Performance Status >= 70;
- Life expectancy of >= 12 weeks;
- Prior radiation therapy provided exposure does not exceed an area of 25% of marrow space
- Adequate hematological function
- Adequate organ function
Exclusion Criteria
- Any available standard line of therapy known to be life-prolonging or life-saving;
- No concurrent therapy or therapy within six weeks of first dose of MEDI-551 for treatment of cancer
- Previous therapy directed against CD19
- Vaccination (other than experimental cancer vaccine therapy) within 28 days prior to receiving the first dose of MEDI-551;
- History of other invasive malignancy within 5 years except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured;
- Active infection requiring treatment
- Autologous stem cell transplantation within 4 months prior to study entry;
- Allogeneic stem cell transplantation or any other organ transplant;
- Ongoing >= Grade 2 toxicities from previous cancer therapies unless specifically allowed in the Inclusion/Exclusion criteria.
- Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551;
- Use of immunosuppressive medication other than steroids within 28 days before the first dose of MEDI-551 (inhaled and topical corticosteroids are permitted);
- Documented current central nervous system involvement by leukemia or lymphoma;
- Pregnancy or lactation;
- Clinically significant abnormality on ECG.
Data sourced from ClinicalTrials.gov (NCT00983619). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.