Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL

NCT02848911 | Terminated Phase 1 DMC

• 1 other identifier: AFM11-102
• Study Type: interventional
• Target: 17
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of the study is to determine the maximum tolerated dose (MTD) in patients with acute lymphoblastic leukemia (ALL) and to determine the safety and tolerability of increasing doses and different infusion times of AFM11 infusion in patients with adult B-precursor ALL

Conditions

Leukemia, B-Cell

Keywords

acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Number of participants with serious and non-serious adverse events as a measure of safety and tolerability of increasing doses and different infusion times of AFM11

  Measure of occurence of adverse events (AEs), laboratory testing (chemistry and hematology), physical examination, vital signs, cardiac monitoring, and neurological assessments

  From first administration of continuous infusion over 2 weeks in step 1 (or 4 weeks in step 2) followed by 2 weeks of treatment break

Secondary Outcomes (4)

• Maximum Plasma Concentration of AFM11 (Cmax)

  Multiple time points during the 2 weeks of treatment in step 1 and 4 weeks of treatment in step 2

• Area Under the Curve (AUC)

  Prior to initial dose on Day 1 and at multiple time points during the 2 weeks of treatment in step 1 and 4 weeks of treatment in step 2

• Clinical efficacy of AFM11 in ALL

  Baseline and after treatment (week 3 in step 1 or week 4 in step 2)

• Measurement of immunological markers

  Prior to initial dose on Day 1 and at multiple time points during the 2 weeks of treatment in Step 1 and 4 weeks of treatment in Step 2

Study Arms (1)

AFM11

EXPERIMENTAL

IV (intravenous) infusion, dose escalation

Drug: AFM11

Interventions

AFM11 DRUG

Accelerated-titration dose-escalation with 1 patient per dose-level, followed by standard dose-escalation (3 + 3 design), Treatment duration: 2 weeks

AFM11

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with CD19+ B-precursor Philadelphia-chromosome negative ALL relapsed after at least induction and consolidation or having refractory disease and who are not candidates for bone marrow transplant (including both peripheral blood and hematopoietic stem cell transplant \[HSCTs\]) with a curative intent at time of screening
• Patients with CD19+ Philadelphia-chromosome positive ALL who failed or were intolerant to therapy with at least 2 approved tyrosine kinase inhibitors
• More than 5% blasts in bone marrow
• In patients with high tumor burden (e.g., more than 50% blasts, or more than 15,000 blasts /µL blood, or elevated lactate dehydrogenase \[LDH\]) \> 2 × upper limit of normal \[ULN\]), a pre treatment with 10 mg/m2 dexamethasone and 200 mg cyclophosphamide could be administered for up to 5 days.
• Patients of both genders, age ≥ 18
• Homogenous CD19 expression on leukemic blasts must be confirmed by either:
• Prior results from a CD19+ staining or flow cytometry at the most recent available diagnostic bone marrow biopsy or aspirate, or
• Submission of a recent bone marrow biopsy for staining for CD19 positivity. The results of this testing need to be available prior to start of AFM11 treatment.
• Eastern Cooperative Oncology Group performance status ≤ 2
• Life expectancy of at least 3 months
• Ability to understand the patient information and informed consent form
• Signed and dated written informed consent

You may not qualify if:

• Autologous HSCT within 3 months prior to start of AFM11 treatment
• Active acute or chronic graft-versus-host disease. All graft-versus-host disease medication should be omitted for at least 4 weeks prior to start of AFM11 treatment.
• Allogeneic HSCT within 3 months prior to start of AFM11 treatment
• Prior treatment with blinatumomab or any other CD19 targeting T-cell engager, including CD19 CAR-T cells
• Treatment with donor-lymphocyte infusions within 4 weeks of start of AFM11 treatment or existing Graft versus Host Disease (GvHD)
• Known or suspected central nervous system (CNS) involvement:
• Evidence for presence of malignant disease, inflammatory lesions, and/or vasculitis on cerebral magnetic resonance imaging (MRI)
• Infiltration of the cerebrospinal fluid by malignant B-cells, confirmed by lumbar puncture
• History of or current relevant CNS pathology as epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis
• Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-lives, whichever is longer
• Therapy with antibody, or antibody constructs within 4 weeks prior to the start of AFM11 treatment, or at least 4 half-lives, whichever is longer
• Treatment with any investigational agent within 4 weeks prior to start of AFM11 treatment, or at least 4 times the respective half-life, whichever is longer
• Contraindication for any of the concomitant medications
• Abnormal renal or hepatic function as follows: aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) ≥ 2.5 × ULN; total bilirubin ≥ 1.5 × ULN; serum creatinine ≥ 2 × ULN; creatinine clearance \< 50 mL/minute
• History of malignancy other than B-cell lymphoma or B-precursor ALL within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix

Sponsors & Collaborators

• Affimed GmbH: lead

Study Sites (12)

LKH-Universitätsklinikum Graz

Graz, Austria

Location

Kepler Universitätsklinikum Linz

Linz, Austria

Location

Uniklinikum Salzburg

Salzburg, Austria

Location

University Hospital

Brno, Czechia

Location

Rambam Medical Center

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Independent Public Healthcare Municipal Hospital

Chorzów, Poland

Location

University Hospital

Krakow, Poland

Location

Baranov Republican Hospital

Petrozavodsk, Russia

Location

First Pavlov State Medical University

Saint Petersburg, 197022, Russia

Location

Almazov NW Federal Medical Research Center

Saint Petersburg, Russia

Location

Related Publications (1)

• Topp M, Dlugosz-Danecka M, Skotnicki AB, Salogub G, Viardot A, Klein AK, Hess G, Michel CS, Grosicki S, Gural A, Schwarz SE, Pietzko K, Gartner U, Strassz A, Alland L, Mayer J. Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies. Trials. 2023 Jan 3;24(1):4. doi: 10.1186/s13063-022-06982-7.

  PMID: 36597128 DERIVED

MeSH Terms

Conditions

Leukemia, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2016
• First Posted: July 29, 2016
• Study Start: October 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: April 1, 2019
• Last Updated: June 19, 2019

Record last verified: 2019-06

Locations

AU (3); RU (3); CZ (1); IL (3); PL (2)