Nordic Nanovector - Fundamentale forhold 2019 (NANO)

anon21766851 · april 13, 2018, 9:52am

Stillingsbeskrivelsen til Luigi?

F-Tosca · april 13, 2018, 1:27pm

Linker fra Frontmasta…
Poster to av dem her.

hsvindle · april 13, 2018, 1:44pm

Oppdatert! Men har ikke hatt tid til å lese.

hsvindle · april 13, 2018, 1:47pm

The page https://clinicaltrials.gov/ct2/show/NCT01796171?term=Betalutin&rank=3 has changed since the previous check.

Changed:

Last Update Posted : September 14, 2017
… into:

Last Update Posted : April 13, 2018

Changed:

positive non-Hodgkin lymphoma. The Phase I part of the study is a dose
escalating study to define the maximum tolerable dose of
(177Lu)-lilotomab (Betalutin), assess safety and toxicity,
pharmacokinetics, biodistribution and efficacy. After completion of the
phase I study, a dose will be selected for the phase II part of the
study which is designed to investigate tumour response rate,
progression free survival, confirmation of the selected dose as well as
safety and toxicity.
… into:

indolent non-Hodgkin lymphoma. Part A of the study included a phase I
dose escalation to define the maximum tolerated / recommended dose for
expansion of (177Lu)-lilotomab (Betalutin), and a phase IIa part to
evaluate safety and preliminary efficacy. Part B of the study will
assess the efficacy and safety of two different Betalutin/lilotomab
dosing regimens in adult patients with relapsed rituximab /
anti-CD20-refractory follicular lymphoma who have received 2 or more
prior therapies.

Changed:

Non-Hodgkin Lymphoma Drug: Betalutin Phase 1 Phase 2
… into:

Non-Hodgkin Lymphoma Follicular Lymphoma Drug: Betalutin Phase 1 Phase
2

Changed:

Estimated Enrollment : 77 participants
Allocation: Non-Randomized
… into:

Estimated Enrollment : 207 participants
Allocation: Randomized

Changed:

Official Title: A Phase I/II Study of (177Lu)-Lilotomab (Betalutin®)
Radioimmunotherapy for Treatment of Relapsed Non-Hodgkin Lymphoma.
… into:

Official Title: A Phase I/II Study of Lutetium (177Lu)-Lilotomab
Satetraxetan (Betalutin®) Antibody-radionuclide-conjugate for Treatment
of Relapsed Non-Hodgkin Lymphoma.

Changed:

Estimated Primary Completion Date : October 2017
Estimated Study Completion Date : December 2021
… into:

Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : March 2025

Added:

Follicular Lymphoma

Changed:

Experimental: With lilotomab pre-dosing
… into:

Experimental: Part A, Arm 1: with lilotomab pre-dosing

Changed:

Dose finding study, starting on 10 MBq/kg b.w. Betalutin
((177Lu)-lilotomab), single injection.
Experimental: Without pre-dosing
… into:

Betalutin, 10 MBq/kg b.w. in escalated doses with 40 mg lilotomab
pre-dosing
Experimental: Part A, Arm 2: without pre-dosing

Changed:

Dose finding study, starting on 10 MBq/kg b.w. Betalutin
((177Lu)-lilotomab), single injection.
Experimental: With rituximab pre-dosing
… into:

Betalutin, 15 MBq/kg b.w. in escalated doses without pre-dosing
Experimental: Part A, Arm 3: with rituximab pre-dosing

Changed:

Dose finding study, starting on 10 MBq/kg b.w. Betalutin
((177Lu)-lilotomab), single injection.
Experimental: Different lilotomab pre-dosing regimen
Betalutin, 15 MBq/kg b.w. in escalated doses with a different lilotomab
… into:

Betalutin, 15 MBq/kg b.w. in escalated doses with rituximab pre-dosing
Experimental: Part A, Arm 4: with higher dose lilotomab pre-dosing
Betalutin, 15 MBq/kg b.w. in escalated doses with a higher dose
lilotomab pre-dosing regimen.
Drug: Betalutin
Betalutin, 15 MBq/kg b.w. in escalated doses with 100 mg/m2 lilotomab
pre-dosing
Experimental: Part A, Arm 5: with intermediate dose lilotomab
pre-dosing
Betalutin, 20 MBq/kg b.w. with an intermediate dose lilotomab

Changed:

Dose finding study, starting on 10 MBq/kg b.w. Betalutin
((177Lu)-lilotomab), single injection.
… into:

Betalutin, 20 MBq/kg b.w. in escalated doses with 60 mg/m2 lilotomab
pre-dosing
Experimental: Part B
Betalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20
MBq/kg b.w. with 100mg/m2 lilotomab
Drug: Betalutin
Betalutin, 15 MBq/kg b.w. with 40mg lilotomab compared to Betalutin, 20
MBq/kg b.w. with 100 mg/m2 lilotomab

Changed:

1. Safety/Dose limiting toxicity [ Time Frame: 12 weeks ]

   Patients are closely monitored during and after injection of

   Betalutin over a 12 week period. Thereafter, at certain intervals

   up to 5 years. Safety evaluations are vital signs, physical

   examination, hematology and serum biochemistry.

   Adverse events and abnormal laboratory values will be graded for

   toxicity according to CTCAE version 4.

Secondary Outcome Measures :

1. Efficacy [ Time Frame: 3 months - 5 years ]

   CT or PET/CT imaging will be used to quantify changes in lesions on

   baseline imaging, with responses classified according to revised

   response criteria for NHL (Cheson, 2007.)

… into:

1. Part A, Phase I [ Time Frame: 12 weeks ]

   To define Maximum tolerated dose (MTD) of Betalutin Adverse events

   and abnormal laboratory values will be graded for toxicity

```
   according to CTCAE version 4.
```

2. Part A, Phase IIa [ Time Frame: 3 months - 5 years ]

   To explore tumour response rates in patients receiving Betalutin

3. Part B, Phase IIb [ Time Frame: 3 months - 5 years ]

```
   Overall response rate
```

Added:

Part A:
Changed:

1. Histologically confirmed (by WHO classification) relapsed incurable

… into:

 * Histologically confirmed (by WHO classification) relapsed incurable

Changed:

```
2. Age ≥ 18 years
```

3. A pre-study WHO performance status of 0-1

4. Life expectancy should be ≥ 3 months

5. <25% tumour cells in bone marrow biopsy

6. Measurable disease by radiological methods

7. Women of childbearing potential must:

     1. understand that the study medication is expected to have

```
        teratogenic risk
```
```
     2. have a negative pregnancy test
```

     3. agree to use, and be able to comply with, effective

        contraception without interruption, 4 weeks before starting

        study drug, throughout study drug therapy and for 12 months

        after end of study drug therapy, even if she has amenorrhoea

8. Male subjects must agree to use condoms during intercourse

   throughout study drug therapy and the following 12 months

9. Patients previously treated with native rituximab are eligible

1. The patient is willing and able to comply with the protocol, and

   agrees to return to the hospital for follow-up visits and

```
   examination
```
1. The patient has been fully informed about the study and has signed
```
   the informed consent form
```

… into:

```
 * Age ≥ 18 years
```

 * A pre-study WHO performance status of 0-1

 * Life expectancy should be ≥ 3 months

 * <25% tumour cells in bone marrow biopsy

 * Measurable disease by radiological methods

Changed:

1. Medical contraindications, including uncontrolled infection, severe

   cardiac, pulmonary, neurologic, psychiatric or metabolic disease,

   uncontrolled asthma/allergy requiring systemic steroids, known HIV

```
   positive
```

2. Laboratory values within 15 days pre-registration:

     1. Absolute Neutrophil Counts (ANC) ≤ 1.5 x 109 /l

     2. Platelet count ≤ 150 x 109 /l

```
     3. Total bilirubin ≥ 30 mmol/l
```

     4. ALP and ALAT ≥ 4x normal level)

     5. Creatinine ≥ 115 µmol/l (men), 97 µmol/l (women))

```
3. Known CNS involvement of lymphoma
```
```
4. Previous total body irradiation
```
```
5. Known history of HAMA
```

6. Chemotherapy or immunotherapy received within the last 4 weeks

… into:

 * Absolute Neutrophil Counts (ANC) ≤ 1.5 x 109 /l

```
 * Platelet count ≤ 150 x 109 /l
```
```
 * Total bilirubin ≥ 30 mmol/l
```
```
 * ALP and ALAT ≥ 4x normal level
```

 * Creatinine ≥ 115 µmol/l (men), 97 µmol/l (women))

```
 * Known CNS involvement of lymphoma
```
```
 * Previous total body irradiation
```
```
 * Known history of HAMA
```

 * Chemotherapy or immunotherapy received within the last 4 weeks

Changed:

```
7. Pregnant or lactating women
```

8. Previous hematopoietic stem cell transplantation (autologous and

… into:

 * Previous hematopoietic stem cell transplantation (autologous and

Changed:

9. Previous treatment with radioimmunotherapy

1. Actively participating in another study or received an

   investigational drug within 4 weeks prior to enrolment

1. Receipt of live, attenuated vaccine within 30 days prior to
  … into:

 * Previous treatment with radioimmunotherapy

 * Receipt of live, attenuated vaccine within 30 days prior to

Changed:

1. Test positive for hepatitis B (HBsAg and anti-HBc)
1. A known hypersensitivity to rituximab, HH1, Betalutin or murine
  … into:

 * Test positive for hepatitis B (HBsAg and anti-HBc)

 * A known hypersensitivity to rituximab, HH1, Betalutin or murine

Added:

Part B:
Inclusion Criteria:

 * Histologically confirmed (by WHO classification) relapsed

   non-Hodgkin B-cell FL (follicular grade I-IIIA).

```
 * Male or female aged ≥ 18 years.
```

 * Received at least 2 prior chemotherapy- or immunotherapy-based

   regimens. Prior therapy must include a rituximab/anti-CD20 agent

   and alkylating agent. Prior exposure to idelalisib or other PI3K

```
   inhibitors is also allowed.
```

 * Patients must be refractory to the last rituximab/anti-CD20 based

   treatment, defined as no response (no CR or PR) during therapy or a

   response (CR/PR) lasting less than 6 months after the completion of

   a regimen of rituximab/anti-CD20 therapy (including occurrence of

   progressive disease (PD) during rituximab/anti-CD20 maintenance

   therapy, or within 6 months of completion of maintenance therapy).

   A previous regimen is defined as one of the following: at least 2

   months of single agent therapy; at least 2 consecutive cycles of

```
   chemotherapy.
```
```
 * WHO performance status of 0-2.
```
```
 * Life expectancy of ≥ 3 months.
```

 * Bone marrow tumour infiltration < 25% (in biopsy taken from a site

```
   not previously irradiated).
```

 * Measurable disease by CT: longest diameter (LDi) > 1.5 cm for nodal

   lesion, LDi > cm for extra nodal lesion within 28 days prior to

```
   start of treatment.
```
```
 * ANC ≥ 1.5 x 109/L.
```
```
 * Platelet count ≥ 150 x 109/L.
```
```
 * Haemoglobin ≥ 9.0 g/dL.
```

 * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (except

   patients with documented Gilbert's syndrome [< 3.0 mg/dL]).

 * Liver enzymes: Aspartate transaminase (AST); Alanine transaminase

   (ALT) or ALP ≤ 2.5 x ULN (or ≤ 5.0 x ULN with liver involvement by

```
   primary disease).
```

 * Adequate renal function as demonstrated by a serum creatinine < 1.5

```
   x ULN.
```
```
 * Negative HAMA test at screening.
```

 * Negative test at screening for Hepatitis B (negative HBsAG and

```
   anti-HBC), Hepatitis C and HIV.
```
Exclusion Criteria:

 * Prior hematopoietic allogenic stem cell transplantation.

 * Prior autologous stem cell transplantation.

 * Evidence of histological transformation from FL to DLBCL at time of

```
   screening.
```
```
 * Previous total body irradiation.
```

 * Prior anti-lymphoma therapy (chemotherapy, immunotherapy or other

   investigational agent) within 4 weeks prior to start of study

   treatment (corticosteroid treatment at doses of ≤ 20 mg/day,

   topical or inhaled corticosteroids, G-CSF or GM-CSF are permitted

   up to 2 weeks prior to start of study treatment). Note: excludes

   pre-treatment with rituximab as part of this study.

 * Patients with known or suspected CNS involvement of lymphoma.

 * History of a previous treated cancer except for the following:

   adequately treated local basal cell or squamous cell carcinoma of

   the skin, cervical carcinoma in situ, superficial bladder cancer,

   localised prostate cancer undergoing surveillance or surgery,

   localised breast cancer treated with surgery and radiotherapy but

   not including systemic chemotherapy, other adequately treated Stage

```
   1 or 2 cancer currently in CR.
```

 * Exposure to another CD37 targeting drug.

 * A known hypersensitivity to rituximab, lilotomab, Betalutin or

   murine proteins or any excipient used in rituximab, lilotomab, or

```
   Betalutin.
```

 * Has received a live-attenuated vaccine within 30 days prior to

```
   enrolment.
```

Changed:

Contact: Laurie Baylor Curtis +44 (0)7950502495
lbaylorcurtis@nordicnanovector.com
… into:

Contact: Clinical Trials clinicaltrials@nordicnanovector.com

Changed:

Recruiting
Linz, Austria, 4020
Recruiting
… into:

Not yet recruiting

Changed:

Recruiting
… into:

Not yet recruiting

Changed:

Recruiting
… into:

Not yet recruiting

Changed:

Recruiting
… into:

Not yet recruiting

Changed:

Recruiting
… into:

Not yet recruiting

Changed:

Not yet recruiting
… into:

Recruiting

Added:

Spain
Recruiting
Madrid, Spain
Recruiting
Salamanca, Spain

Changed:

Last Update Posted: September 14, 2017
Last Verified: September 2017
… into:

Last Update Posted: April 13, 2018
Last Verified: April 2018
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Added:

Lymphoma, Follicular

Added:

Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

------------------- End of page report ---------------

Fornybar · april 13, 2018, 1:56pm

Jess! Det ser da ut som om

PARADIGME GODKJENT AV FDA OG OPPDATERT PÅ CLINICALTRIALS.ORG !!!

anon21766851 · april 13, 2018, 2:15pm

Gledelig!

Er det slik at oppdatering av clinicaltrials er synonymt med FDA-godkjenning?

Så denne disclaimeren på toppen.

Fornybar · april 13, 2018, 2:17pm

Jeg tolker det som om de 100% ikke forventer noen flere spørsmål. At least.

sparkonge · april 13, 2018, 2:25pm

Jeg er på tlf, så mulig det er derfor jeg ikke ser det, men hva er det i dagens oppdatering på clinicaltrials.gov som indikerer at FDA har godkjent PARADIGME?

robertih · april 13, 2018, 2:33pm

Er det noen som husker/vet når de første landene åpnet for rekruttering?

tony · april 13, 2018, 2:38pm

1.februar ble kommunisert (Lisa) dagen da Costa gikk av.

Oilimp · april 13, 2018, 2:41pm

Hva mener du med den setningen?

tony · april 13, 2018, 2:44pm

Som svar til Robertih

F-Tosca · april 13, 2018, 2:47pm

Dette, kanskje? Men da burde det jo vært meldt

amagad · april 13, 2018, 2:52pm

Ser ut til å stemme, men hvorfor skulle det vært meldt? De melder vel FPD og ikke hver enkelt godkjenning.

Fornybar · april 13, 2018, 2:57pm

Det er vel eeeegentlig ikke noe mer enn at siden er oppdatert, det er kommunisert at det ikke var noen spørsmål fra FDA etter review, og at sites var forventet å åpne mid year, det vil si noen måneder etter godkjenning. Og at NANO velger å publisere den i dag.

F-Tosca · april 13, 2018, 3:01pm

Mulig det. Bare litt lei infotørke.

Kark17 · april 13, 2018, 5:28pm

Bingo! Endelig! Se samme link. Samarbeidspartner, ICON Clinical Research, antall pasienter er 207, altså seamless design (77 +130). Og status er RECRUITING! Og da må det vel være godkjent av FDA…eller?
Så når vil dette gjenspeiles i kursen?

Fornybar · april 13, 2018, 5:50pm

En ting er at det ikke er 100% sikkert at FDA har godkjent, ENDA, en annen ting er at de har endret 37-01 til å inneholde 207 pasienter. Det betyr at de har fortsatt å inkludere til fase 1/2 av etiske hensyn mens REK har vært kranglevoren.

På ASH var det innrullert 64 pasienter, hvorav 25 i arm 1 og 12 i arm4. De har nå 13 ekstra pasienter. Det kan se ut som om vi får like stort datasett på arm 1 og arm 4 til ASH18.

Symmetrisk og pent.

anon21766851 · april 13, 2018, 6:10pm

Denne slutningen syns jeg virker veldig prematur.

Kan du utbrodere mer? 37-01 var stengt og lukket for innrullering, og at de ventet avlesning på de siste.

At tallet er 207 tror jeg bunner ut i at de BUDSJETTERTE med 77 pasienter i 37-01(ihht. studieoppsettet før oppdatering av clinicaltrials). Tallet er ish, og kan ikke tolkes regelrett. Tror jeg.

Men for all del, hadde vært fenomenalt om de har innrullert i mellomtiden.

larsmkn · april 13, 2018, 6:04pm

Jeg tror ikke FDA godkjenner studien i den forstand som REK i Norge. De godkjenner om du kan gjøre kliniske studier, men etter det så er det mer enn dialog enn at du trenger godkjenning for hver nye fase du starter opp.
Ref: https://www.fda.gov/ForPatients/Approvals/Drugs/ucm405622.htm