Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007276

Trial Description

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Title

A Pharmacodynamically-guided, Dose-escalation, Phase I Study to Assess the Safety of AFM11 (Recombinant Antibody Construct Against Human CD19 and CD3) in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL and Adult B-precursor ALL.

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

The purpose of this study is to determine whether AFM11 is safe and active in the treatment
of relapsed and/or refractory Non-Hodgkin Lymphoma (NHL) and Acute Lymphoblastic Leukemia
(ALL).

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Brief Summary in Scientific Language

CD19 is present on B-cells from earliest recognizable B-lineage cells during development to
B-cell blasts and is lost only upon maturation to plasma cells. Expression of CD19 on
B-cells at various development stages makes it an ideal target to treat B-cell associated
malignancies, like Non-Hodgkin's lymphoma and Acute lymphoblastic leukemia.The rationale for
the use of AFM11 is based on its ability to bind to both malignant cells via its anti-CD19
domain and to T-cells via its anti-CD3 domains. This results in the formation of the
"immunological synapse" and the subsequent T-cell activation on leading to killing of
malignant cells.

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Organizational Data

  •   DRKS00007276
  •   2016/04/15
  •   2014/04/01
  •   no
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Secondary IDs

  •   2013-001919-78 
  •   NCT02106091  (ClinicalTrials.gov)
  •   AFM11-101  (Affimed Therapeutics AG)
  •   2013-001919-78 
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Health Condition or Problem studied

  •   Relapsed B-Cell Non-Hodgkin Lymphoma
  •   Refractory B-Cell Non-Hodgkin Lymphoma
  •   Relapsed Adult B-Precursor Acute Lymphoblastic Leukemia
  •   Refractory Adult B-Precursor Acute Lymphoblastic Leukemia
  •   C83 -  Non-follicular lymphoma
  •   C91 -  Lymphoid leukaemia
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Interventions/Observational Groups

  •   Drug: AFM11
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I
  •   [---]*
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Primary Outcome

- Number of participants with serious and non-serious adverse events as a measure of safety and tolerability of AFM11.; time frame: From administration of the first dose of study drug and through 30 days after the last dose, up to 8 weeks.; Measure occurence of adverse events until the Final Study Visit and monitor laboratory safety parameters at least once weekly. Assess immunogenicity of AFM11 at end of treatment cycle.

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Secondary Outcome

- Maximum Tolerated Dose (MTD) or Optimal Biological Dose (OBD) of AFM11.; time frame: up to 8 weeks
- Pharmacokinetic profile of AFM11and immunological markers of AFM11 activity.; time frame: Prior to initial dose on Day 1 and at multiple time points during the 4 weeks of treatment until up to 30 days after the last dose.; Concentration of AFM11 in blood samples will measured at different time points during the 4 weeks of treatment and 30 days thereafter to determine concentration-time profiles. Immunological markers like lymphocytes, cytokine and complement levels in serum will be measured at different time points during the 4 weeks of treatment and 30 days thereafter to assess the level of activity resulting from administration of AFM11.
- Tumor Response.; time frame: Baseline and at week 8.; Measure tumor size and activity in FDG-PET and CT-scans.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

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  •   2014/04/30
  •   40
  •   Multicenter trial
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Inclusion Criteria (NHL patients):

- Patients with CD19+, relapsed or refractory histologically (WHO classification)
confirmed follicular lymphoma, marginal zone lymphoma, lymphoplasmocytic lymphoma,
mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal B-cell lymphoma, or
transformed B-cell lymphomas.

- Patients with either indolent or aggressive NHL.

- Patients who relapsed or were refractory to the approved standard therapy, which must
have included 1 treatment line with rituximab plus chemotherapy, and who are not
candidates for bone marrow transplant with a curative intent.

- Measurable disease (at least 1 lesion ≥ 1.5 cm) documented by CT scan.

- Disease progression requiring therapy.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.


Inclusion Criteria (ALL patients):

- Patients with CD19+ B-precursor ALL relapsed after at least induction and
consolidation or having refractory disease and who are not candidates for bone marrow
transplant with a curative intent.

- More than 5% blasts in bone marrow.

- In patients with high tumor burden (e.g. more than 50% blasts, elevated lactate
dehydrogenase [LDH]) greater than 2-fold ULN, or signs of extramedullar involvement),
a pre-treatment with 10 mg/m² dexamethasone is required for up to 5 days.

- Patients with Philadelphia positive ALL who failed or were intolerant to therapy with
at least 2 approved tyrosine kinase inhibitors.

- Eastern Cooperative Oncology Group performance status ≤ 2.


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Exclusion Criteria

Exclusion Criteria (NHL patients):

- Total number of B-cells (healthy and malignant combined) in the peripheral blood
exceeds the upper physiological limit (as per institutional guidance) of total B-cell
counts in healthy individuals.

- Autologous Hematopoietic stem cell transplant (HSCT) within 3 months prior to start
of AFM11 treatment.

- Prior allogeneic HSCT.

- Abnormal hematological laboratory values as defined below:

1. Peripheral lymphocyte count > 20 × 10^9/L

2. Platelet count ≤ 75,000/µL

3. Hemoglobin level ≤ 9 g/dL.

- Known or suspected central nervous system (CNS) involvement.

1. History of or current relevant CNS pathology as epilepsy, seizure, paresis,
aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain
syndrome, psychosis.

2. Evidence for presence of malignant disease, inflammatory lesions, and/or
vasculitis on cerebral MRI.

3. Infiltration of the cerebrospinal fluid by malignant B-cells, confirmed by
lumbar puncture.

- Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4
times the respective half-lives, whichever is longer.

- Radiotherapy within 4 weeks prior to start of AFM11 treatment.

- Therapy with antibody, or antibody constructs within 4 weeks prior to start of AFM11
treatment, or at least 4 times the respective half-lives, whichever is longer.

- Prior treatment with alemtuzumab (Campath®) within 3 months prior to start of AFM11
treatment.

- 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.

- Abnormal renal or hepatic function as follows: aspartate aminotransferase (AST or
serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT
or serum glutamic pyruvic transaminase [SGPT]) ≥ 2.5 × upper limit of normal (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.

- Uncontrolled infections; known bacteremia.

- Regular dose of corticosteroids during the 4 weeks prior to start of AFM11 treatment
of this study or anticipated need of corticosteroids exceeding prednisone 20 mg/day
or equivalent, or any other immunosuppressive therapy within 4 weeks prior to start
of AFM11 treatment.

- Known infection with human immunodeficiency virus (HIV) or chronic infection with
hepatitis B or hepatitis C virus.

- Pregnant or nursing women or women of childbearing potential not willing to use an
effective form of contraception during participation in the study and at least 3
months thereafter. Male patients not willing to ensure that during the study and at
least 3 months thereafter no fathering takes place.

- Patients with B-cell chronic lymphocytic leukemia, small lymphocytic lymphoma, and
Waldenström's macroglobulinemia.


Exclusion Criteria (ALL patients):

- 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.

- No treatment with donor-lymphocyte infusions within 3 months of start of AFM11
treatment.

- Abnormal hematological laboratory values as defined below:

1. Platelet count ≤ 20,000/µL

2. Hemoglobin level ≤ 9 g/dL.

- Known or suspected CNS involvement.

1. History of or current relevant CNS pathology as epilepsy, seizure, paresis,
aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain
syndrome, psychosis.

2. Evidence for presence of malignant disease, inflammatory lesions, and/or
vasculitis on cerebral MRI.

3. Infiltration of the cerebrospinal fluid by malignant B-cells, confirmed by
lumbar puncture.

- Cancer chemotherapy within 4 weeks prior to start of AFM11 treatment, or at least 4
times the respective half-lives, whichever is longer.

- Radiotherapy within 4 weeks prior to start of AFM11 treatment.

- Therapy with antibody, or antibody constructs within 4 weeks prior to start of AFM11
treatment, or at least 4 times the respective half-lives, whichever is longer.

- Prior treatment with alemtuzumab (Campath®) within 3 months prior to start of AFM11
treatment.

- 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.

- Abnormal renal or hepatic function as follows: AST (or SGOT) and/or 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.

- Uncontrolled infections; known bacteremia.

- Regular dose of corticosteroids during the 4 weeks prior to start of AFM11 treatment
of this study or anticipated need of corticosteroids exceeding prednisone 20 mg/day
or equivalent, or any other immunosuppressive therapy within 4 weeks prior to study
entry.

- Known infection with HIV or chronic infection with hepatitis B or hepatitis C virus.

- Pregnant or nursing women or women of childbearing potential not willing to use an
effective form of contraception during participation in the study and at least 3
months thereafter. Male patients not willing to ensure that during the study and at
least 3 months thereafter no fathering takes place.

- Patients with B-cell chronic lymphocytic leukemia, small lymphocytic lymphoma, and
Waldenström's macroglobulinemia.

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Addresses

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    • Affimed Therapeutics AG
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    •   [---]*
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  • start of 1:1-Block address scientific-contact
    • Gudrun Beck 
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    • Gudrun Beck 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/11/05
* This entry means the parameter is not applicable or has not been set.