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

Phase 1

• Conditions: Relapsed/Refractory Precursor B-cell or T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma; MedDRA version: 21.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10066109Term: Precursor B-lymphoblastic leukemia acuteSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10066110Term: T-cell lymphoblastic leukemia acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003377-34-NL
• Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-07
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

Each potential subject must satisfy all the following criteria to be enrolled in the study:
1. =1 and =30 years of age
2. Documented ALL or LL as defined by the criteria below:
a) B-cell cohort:
Stage 1:
- ALL in second or greater relapse or refractory to 2 prior induction
regimens with =5% blasts in the bone marrow and aged 1 to <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
b) 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
3. Performance status =70 by Lansky scale (for subjects <16 years of age) or Karnofsky scale (for subjects =16 years of age)
4. Adequate hematology laboratory values at Cycle 1 Day 1 pre-dosing defined as follows:
a. Hemoglobin =7.5 g/dL (=5 mmol/L; prior red blood cell [RBC] transfusion is permitted)
b. Platelet count =10 × 109/L (prior platelet transfusion is permitted)
5. Adequate renal function defined as normal serum creatinine for the subject’s age or creatinine clearance or radioisotope glomerular filtration rate (GFR) =70 mL/min/1.73 m2 prior to enrollment (see Attachment 3).
6. Adequate liver function prior to enrollment defined as:
a. Alanine aminotransferase level =2.5x the upper limit of normal (ULN)
b. Aspartate aminotransferase level =2.5xULN, and
c. Total bilirubin =2x ULN or direct bilirubin level =2.0xULN
7. Female subjects of childbearing potential (defined as post-menarchal and sexually active until becoming post menopausal unless permanently sterile) must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously during the Treatment Period, during any dose
interruptions, and for 12 months after the last dose of any component of the treatment regimen. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drug. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject. Birth control methods must include one highly effective method of contraception (tubal ligation, intrauterine device, hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants], or partner’s vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing. Reliable
contraception is indicated even where there has been a history of infertility, unless due to hysterectomy.
8. During the study and for 12 months after receiving the last dose of any component of the treatment regimen, femal

Exclusion Criteria

Any potential subject who meets any of the following criteria will be excluded from participating in the study:
1.Received an allogeneic hematopoietic transplant within 3 months of screening
2Active acute graft-versus-host disease of any grade or chronic graft-versus-host disease of Grade 2 or higher
3.Received immunosuppression post hematopoietic transplant within 1 month of study entry.
4.Philadelphia chromosome positive (Ph+) B-cell ALL eligible for tyrosine kinase inhibitor therapy
5.Has either of the following:
a. Evidence of dyspnea at rest or oxygen saturation =94%.
b.Known moderate or severe persistent asthma within the past 2 years,or uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma may participate in the study
6.Down syndrome, juvenile myelomonocytic leukemia,Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome
7.Prior exposure to daratumumab or other anti-CD38 therapies
8.Prior cancer immunotherapy (ie, CAR-T, inotuzumab) within 4 weeks prior to enrollment or blinatumomab within 2 weeks prior to enrollment.
9.For subjects with T-cell ALL/LL only: prior cumulative anthracycline exposure must not exceed 400 mg/m^2 of doxorubicin or equivalent
10.Subject is:
?known to be seropositive for human immunodeficiency virus (HIV)
?seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]).Subjects with resolved infection (ie,subjects 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) DNA levels.Those who are PCR positive will be excluded. EXCEPTION:
Subjects with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
?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)
11.Screening 12-lead electrocardiogram (ECG) showing a baseline QT interval >470 msec or Grade 3 or higher cardiac disorders (according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03)
12.Known allergies,hypersensitivity,or intolerance to mannitol, glucocorticoid,methotrexate, vincristine, mAb (IRR is not considered hypersensitivity) or human proteins, or their excipients (refer to respective package inserts and Investigator’s Brochure),or known sensitivity to mammalian-derived products.For subjects with Tcell ALL/LL only,known allergies to doxorubicin,cytarabine,cyclophosphamide,or 6-mercaptopurine.
13.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
14.Pregnant,breastfeeding,or planning to become pregnant while enrolled in this study or within 12 months after the last dose of any component of the treatment regimen
15.Plans to father a child while enrolled in this study or within 6 months after the last dose of any component of the treatment regimen
16.Subject has any concurrent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified