JOURNAL ONKOLOGIE – STUDIE

Sabatolimab as a Treatment for Patients With Acute Myeloid Leukemia and Presence of Measurable Residual Disease After Allogeneic Stem Cell Transplantation.

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04623216

Studienbeginn:
September 2021

Letztes Update:
03.05.2024

Wirkstoff:
Sabatolimab, azacitidine

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute, Neoplasm, Residual

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Novartis Pharmaceuticals
Kontakt:
Phone: 1-888-669-6682
E-Mail: novartis.email@novartis.com» Kontaktdaten anzeigen

Novartis Pharmaceuticals
Kontakt:
Phone: +41613241111
» Kontaktdaten anzeigen

Studienlocations
(3 von 14)

Novartis Investigative Site
79106 Freiburg
(Baden-Württemberg)
GermanyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
20246 Hamburg
(Hamburg)
GermanyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
04103 Leipzig
(Sachsen)
GermanyZurückgezogen» Google-Maps

Novartis Investigative Site
48149 Muenster
(Nordrhein-Westfalen)
GermanyAbgeschlossen» Google-Maps

Novartis Investigative Site
13273 Marseille
FranceAbgeschlossen» Google-Maps

Novartis Investigative Site
75475 Paris 10
FranceZurückgezogen» Google-Maps

Novartis Investigative Site
24128 Bergamo
ItalyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
40138 Bologna
ItalyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
25123 Brescia
ItalyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
00165 Roma
ItalyAktiv, nicht rekrutierend» Google-Maps

Novartis Investigative Site
37007 Salamanca
SpainZurückgezogen» Google-Maps

Novartis Investigative Site
08035 Barcelona
SpainAbgeschlossen» Google-Maps

Novartis Investigative Site
35010 Las Palmas de Gran Canaria
SpainRekrutierend» Google-Maps

Novartis Investigative Site
28009 Madrid
SpainZurückgezogen» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

This is a phase Ib/II, open label, multi-center study of sabatolimab as monotherapy and in

combination with azacitidine, in participants with AML/secondary AML who have received one

aHSCT and achieved complete remission but MRD+, by local assessment, anytime between day 100

and day 365 post-aHSCT and at least 2 weeks after immunosuppressive medications have been

tapered off.

The study will enroll approximately 59 participants and will be conducted in two parts:

Part 1 is a Safety Run-in of approximately 20 participants, to assess whether sabatolimab as

monotherapy at the two tested dose levels (400 mg and 800 mg intravenously Q4W) is safe when

administered in the post-aHSCT setting. For each dose level, once the required number of

evaluable participants has been confirmed, enrollment will be halted until participants have

completed the DLT observation period (≥ 8 weeks following the first dose). Following the

observation period for DLTs, a Safety Review Meeting will be conducted after each dose level

to assess safety and determine the recommended dose for expansion to proceed with enrollment

of additional cohorts in Part 2 of the study.

Part 2 consists of sabatolimab monotherapy expansion cohort of approximately 13 participants,

sabatolimab in combination with azacitidine cohort of approximately 20 participants, and an

adolescent cohort of approximately 6 participants (≥ 12 years but < 18 years of age) with

sabatolimab as monotherapy. Sabatolimab will be administered at the recommended dose for

expansion determined in Part 1.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.

2. At the date of signing the informed consent form (ICF), eligible participants must be

≥ 18 years for the adult cohorts; and ≥ 12 years old but < 18 years old for the

adolescent cohort (cohort 5), which will open after completion of Safety Run-in.

3. Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML

4. Participants in complete remission (< 5% bone marrow blasts, absence of circulating

blasts, and absence of extramedullary disease) with measurable residual disease (MRD)

positivity by local assessment, at any time between day 100 and day 365 after

allogeneic stem cell transplantation.

5. Ability to provide a fresh bone marrow aspirate sample collected within 28 days from

enrollment/randomization, and immediately shipped to a Novartis designated central

laboratory for MRD testing.

6. Systemic GvHD (graft versus host disease) prophylaxis or treatment [immunosuppressive

treatment (IST)] completely tapered for at least two weeks prior to study entry.

Prednisone dose ≤ 5 mg/day or equivalent corticosteroid dose is allowed.

7. Participants who are found with MRD positivity while still on or tapering systemic

GvHD prophylaxis or treatment, MRD positivity must be re-confirmed at least 2 week

after the last dose of IST

8. For the adult cohorts, participants must have an Eastern Cooperative Oncology Group

(ECOG) performance status of 0, 1 or 2.

For the adolescent cohort, participants must have a Karnofsky (age ≥ 16 years) or Lansky

(age < 16 years) performance status score ≥ 50%.

Exclusion Criteria:

1. Prior exposure to TIM-3 directed therapy at anytime.

2. History of severe hypersensitivity reactions to any ingredient of study drug(s)

(azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients

3. Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is

controlled under antiviral therapy should not be excluded.

4. Active acute GvHD grade III-IV according to standard criteria (Harris 2016).

5. Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active

severe chronic GvHD according to NIH consensus criteria.

6. History of another primary malignancy that is currently clinically significant or

currently requires active intervention.

7. Any concurrent severe and/or active uncontrolled infection requiring parenteral

antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis,

or septicemia)

8. Active autoimmune disease requiring systemic therapy (e.g. corticosteroids). Topical,

inhaled, nasal and ophthalmic steroids are not prohibited. Replacement corticosteroids

therapy is allowed and not considered a form of systemic treatment

9. Live vaccine administered within 30 days prior to the first day of study treatment

(Cycle 1 Day 1)

10. Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled

diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease

including dyspnoea at rest from any cause) or history of serious organ dysfunction or

disease involving the heart, kidney, or liver

Other protocol defined inclusion/exclusion criteria may apply

Studien-Rationale

Primary outcome:

1. Incidence of dose limiting toxicities (Safety Run-in in adult cohorts 1 and 2 only) (Time Frame - From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days):
Assessment of tolerability of sabatolimab in adults in the post allogenic stem cell transplantation setting

2. Percentage of adult subjects with absence of hematologic relapse per Investigator assessment (Safety Run-in and Expansion) (Time Frame - From cycle 1day 1 to end of cycle 6, cycle =28 Days)):
Assessment of Complete Remission Maintenance Rate (no evidence of bone marrow blasts ≥5%; no evidence of reappearance of blasts in the blood; no evidence of development of extramedullary disease)

3. Incidence of dose limiting toxicities (Safety confirmation in adolescent cohort 5 only) (Time Frame - From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days):
Assessment of tolerability of sabatolimab in adolescent patients in the post allogeneic stem cell transplantation setting

Secondary outcome:

1. Incidence of grade III or IV acute Graft versus Host Disease (aGvHD) (Time Frame - From start of treatment to up to 36 months from last patient first treatment.):
Assessment of the treatment emergent grade III or IV aGvHD.

2. Incidence of moderate to severe Chronic GVHD (cGvHD) (Time Frame - From start of treatment to up to 36 months from last patient first treatment.):
Assessment of the treatment emergent moderate or severe cGvHD.

3. Peak of Serum Concentration (Cmax) sabatolimab (Time Frame - Cycle 1 day1 or day 5 (end of infusion) and cycle 3 day 1 or day 5(end of infusion) for adult cohorts and cycle 1 day 1 (end of infusion) and cycle 3 day 1(end of infusion) for adolescent cohort, cycle =28 days):
Maximal serum concentration of sabatolimab

4. Trough serum concentration (Cmin) sabatolimab (Time Frame - Day 1 or Day 5 of cycle 1, 3, 6 and 24 for adult cohorts and day 1 of Cycle 1, 2, 3, 6, 9, 12, 18 and 24 for adolescent cohort, and through treatment completion, an average of 15 months; cycle=28 days):
Concentration of sabatolimab prior to next dosing or after end of treatment.

5. Anti-drug antibody (ADA) prevalence on-treatment (Time Frame - Throughout study until 150 day safety follow-up):
Immunogenicity to sabatolimab on treatment and after treatment.

6. ADA prevalence at baseline (Time Frame - prior to first dose of sabatolimab on cycle 1 cycle= 28 days):
Immunogenicity to sabatolimab prior to sabatolimab exposure

7. Time from start of treatment to the date of first documented GvHD- free/ relapse- free survival (Time Frame - Every 2 weeks until week 9 then every 4 weeks until week 25, and then every 8 weeks until end of treatment, and then every 12 weeks for up to 36 months from last patient first treatment.):
Time from start of treatment to the date of first documented occurrence or worsening of treatment emergent grade III or IV aGvHD or moderate to severe cGvHD requiring initiation of systemic treatment, morphologic/hematologic relapse, or death due to any cause, whichever occurs first

8. Time from start of treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first (Time Frame - Every 4 weeks (starting on week 5) until week 13, then every 12 weeks until week 49 and every 24 weeks thereafter up to 36 months from last patient first treatment):
Time to relapse from complete remission (CR/CRi) or death whichever occurs first

9. Incidence of grade 3 immune-related adverse events not attributed to GvHD (Time Frame - Throughout the study until 150 day safety follow up period):
Assessment of severe immune-related adverse events not attributed to GvHD

10. Percentage of participants with measurable residual disease (MRD) positive at baseline who become MRD negative (Time Frame - From start of treatment until end of cycle 6 (cycle = 28 Days)):
MRD conversion rate

Studien-Arme

Experimental: Sabatolimab 400mg
Safety cohort 1: Participants in this arm will receive sabatolimab 400mg intravenously every 4 weeks.
Experimental: Sabatolimab 800mg
Safety cohort 2: Participants in this arm will receive sabatolimab 800mg intravenously every 4 weeks.
Experimental: Sabatolimab + Azacitidine
Expansion cohort 3: Participants in this arm will receive sabatolimab at the recommended dose for expansion in combination with azacitidine.
Experimental: Sabatolimab
Expansion cohort 4: Participants in this arm will receive sabatolimab at the recommended dose for expansion.
Experimental: Sabatolimab (adolescent cohort)
Adolescent safety cohort (cohort 5): ≥12 to < 18 year old adolescent participants in this arm will receive sabatolimab at the recommended dose for expansion.

Geprüfte Regime

Sabatolimab (MBG453):
Sabatolimab is a solution in vial for IV infusion
Azacitidine:
Azacitidine comes in Vial for IV infusion or subcutaneous administration

Quelle: ClinicalTrials.gov

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