Clinical trial NCT03384654: A Study to Evaluate the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Participants Greater Than or Equal to (>=)1 and Less Than or Equal to (<=) 30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Official title: An Open-label, Multicenter, Phase 2 Study Evaluating the Efficacy and Safety of Daratumumab in Pediatric and Young Adult Subjects >=1 and <=30 Years of Age With Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-12-27
Enrollment: 47
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of daratumumab in addition to standard chemotherapy in pediatric participants with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LL) and T-cell ALL/LL as measured by the complete response (CR) rate.

Detailed description: Screening for eligible participants will be performed within 21 days before administration of the study drug. Participants with B-cell ALL/LL will receive treatment until disease progression, unacceptable toxicity or achievement of CR followed by hematopoietic stem cell transplant (HSCT). Participants with T cell ALL/LL will receive treatment for up to 2 cycles. If disease progression is confirmed, then the participant will discontinue study treatment, complete the End of Treatment Visit, and enter the Posttreatment Period. For those participants who discontinue study drug prior to disease progression, disease evaluations will continue to be performed every 8 weeks until subsequent anticancer therapy is initiated.

Eligibility criteria: Inclusion Criteria:

* Documented acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) as defined by the criteria below:

  1. B-cell cohort: Stage 1; ALL in second or greater relapse or refractory to 2 prior induction regimens with greater than or equal to (\>=) 5 percent (%) blasts in the bone marrow and aged 1 to less than (\<) 18 years. Stage 2; ALL in second or greater relapse or refractory to 2 prior induction regimens with (\>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in second or greater relapse or refractory to 2 prior induction regimens and biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years.
  2. T-cell cohort: Stage 1; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (\>=) 5% blasts in the bone marrow and aged 1 to \<18 years. Stage 2; ALL in first relapse or refractory to 1 prior induction/consolidation regimen with (\>=) 5% blasts in the bone marrow and aged 1 to 30 years. LL in first relapse or refractory to 1 prior induction/consolidation regimen biopsy proven and with evidence of measurable disease by radiologic criteria and aged 1 to 30 years
* Performance status greater than or equal to (\>=) 70 by Lansky scale (for participants less than \[\<\] 16 years of age) or Karnofsky scale (for participants \[\>=\] 16 years of age)
* Adequate hematology laboratory values at Cycle 1 Day 1 pre-dosing defined as follows:

  1. Hemoglobin (\>=) 7.5 gram per deciliter (g/dL) (\[\>=\] 5 millimole per liter \[mmol/L\]; prior red blood cell \[RBC\] transfusion is permitted)
  2. Platelet count (\>=) 10\*10\^9 per liter (L) (prior platelet transfusion is permitted)
* Adequate renal function defined as normal serum creatinine for the participant's age or creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) prior to enrollment
* Adequate liver function prior to enrollment defined as:

  1. Alanine aminotransferase level less than or equal to (\<=) 2.5\* the upper limit of normal (ULN),
  2. Aspartate aminotransferase level (\<=) 2.5\* ULN, and
  3. Total bilirubin (\<=) 2\* ULN or direct bilirubin level (\<=) 2.0\* ULN

Exclusion Criteria:

* Received an allogeneic hematopoietic transplant within 3 months of screening
* Active acute graft-versus-host disease of any grade or chronic graft-versus-host disease of Grade 2 or higher
* Received immunosuppression post hematopoietic transplant within 1 month of study entry
* Philadelphia chromosome positive (Ph+) B-cell ALL eligible for tyrosine kinase inhibitor therapy
* Has either of the following:

  1. Evidence of dyspnea at rest or oxygen saturation (\<=) 94 percent (%).
  2. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
* Received an investigational drug, was vaccinated with live attenuated vaccines, or used an invasive investigational medical device within 4 weeks before the planned first dose of study drug, or is currently being treated in an investigational study
* Known to be seropositive for human immunodeficiency virus (HIV)
* Any one of the following:

  1. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (ie, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[anti-HBc\] and/or antibodies to hepatitis B surface antigen \[anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded
  2. Known to be seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy)

Primary outcomes:
measure: Cohort 1: Percentage of Participants With Complete Response (CR) for B-cell Acute Lymphoblastic Leukemia (ALL)
timeFrame: Up to 2 cycles, that is, up to 56 days (each cycle of 28-days)
measure: Cohort 2: Percentage of Participants With Complete Response (CR) for T-cell ALL
timeFrame: End of Cycle 1 (that is, up to 28 days)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 years 4 months
measure: Event-free Survival (EFS)
timeFrame: Up to 4 years 4 months
measure: Relapse-free Survival (RFS)
timeFrame: Up to 4 years 4 months
measure: Overall Survival (OS)
timeFrame: Up to 4 years 4 months
measure: Minimal Residual Disease (MRD) Negative Rate
timeFrame: Up to 4 years 4 months
measure: Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
timeFrame: Up to 4 years 4 months
measure: Maximum Observed Serum Concentration (Cmax) of Daratumumab
timeFrame: Cohort 1: B-cell ALL: End of infusion (EOI) on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): EOI on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): EOI on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): EOI on Day 22 of Cycle 2
measure: Minimum Observed Serum Concentration (Cmin) of Daratumumab
timeFrame: Cohort 1: B-cell ALL: Predose on Day 1 of Cycle 2; Cohort 2: T-cell ALL (1-17 years): Predose on Day 22 of Cycle 2; Cohort 2: T-cell ALL (18-30 years): Predose on Day 1 of Cycle 2; Cohort 2: T-cell LL (1-30 years): Predose on Day 22 of Cycle 2
measure: Number of Participants With Anti-daratumumab Antibodies
timeFrame: Up to 4 years 4 months
measure: Concentration of Daratumumab in Cerebrospinal Fluid (CSF)
timeFrame: Pre-dose on Cohort 1: Cycles 1 and 2: Day 1; Cohort 2: Cycle 1 Day 1 and Day 15 and Cycle 2 Day 2 and Day 15
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital Orange County
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Atlanta
country: United States
facility: Children'S Healthcare Of Atlanta/Emory Univ. Dept. Of Pediatrics
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington Univeristy School of Medicine/ Pediatrics
state: Missouri
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas/Children's Blood and Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Primary Children's Medical Center
state: Utah
city: Milwaukee
country: United States
facility: Medical College Of Wisconsin
state: Wisconsin
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - UZ GENT
city: Bordeaux
country: France
facility: CHU de Bordeaux, Hopital des Enfants
city: Lyon
country: France
facility: IHOPE - Hospices civils de Lyon
city: Paris
country: France
facility: Hopital trousseau- APHP
city: Paris
country: France
facility: Hôpital Robert Debré
city: Vandoeuvre les Nancy
country: France
facility: Hôpital D'Enfants
city: Berlin
country: Germany
facility: Charite-Universitätsmedizin Berlin - Berlin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Münster
country: Germany
facility: Universitatsklinikum Munster
city: Petach Tiquva
country: Israel
facility: Schneider Children's Medical Center
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Monza
country: Italy
facility: Fondazione MBBM, ASST Monza
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambin Gesù
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino, Presidio Ospedale Infantile Regina Margherita
city: Utrecht
country: Netherlands
facility: Princess Maxima Center
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Esplugues de Llobregat
country: Spain
facility: Hosp. Sant Joan de Deu
city: Madrid
country: Spain
facility: Hosp. Infantil Univ. Nino Jesus
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
city: Leeds
country: United Kingdom
facility: Leeds Children's Hospital
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Surrey
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Ruhayel SD, Valvi S. Daratumumab in T-cell acute lymphoblastic leukaemia: A case report and review of the literature. Pediatr Blood Cancer. 2021 May;68(5):e28829. doi: 10.1002/pbc.28829. Epub 2020 Nov 27. No abstract available.