Trial Title:
A Phase 2 Study to Evaluate Efficacy of Calaspargase Pegol-mknl and Decitabine Combined With Venetoclax in Pediatric, Adolescent, and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL) and T- Cell Lymphoblastic Lymphoma (T-LLy)
NCT ID:
NCT06561074
Condition:
T-cell Acute Lymphoblastic Leukemia
T-Cell Lymphoblastic Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Venetoclax
Decitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Decitabine
Description:
Given by vein
Arm group label:
Treatment w/Calaspargase pegol-mknl + Decitabine + Venetoclax
Other name:
Dacogen
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given by mouth
Arm group label:
Treatment w/Calaspargase pegol-mknl + Decitabine + Venetoclax
Other name:
ABT-199, GDC-0199
Intervention type:
Drug
Intervention name:
Calaspargase pegol-mknl
Description:
Given by vein
Arm group label:
Treatment w/Calaspargase pegol-mknl + Decitabine + Venetoclax
Summary:
To learn if giving the study drugs calaspargase pegol-mknl and decitabine in combination
with venetoclax can help to control relapsed/refractory T-ALL and T-LLy. The safety of
this drug combination will also be studied.
Detailed description:
Primary Objectives:
To characterize the clinical efficacy of Calaspargase pegol-mknl and Decitabine in
combination with Venetoclax in pediatric, adolescent, and young adult patients with
relapsed/refractory T-ALL/T-LLy based upon the complete response rate (CR).
Secondary Objectives:
To summarize efficacy per response rate, overall survival (OS), event free survival
(EFS), and minimal residual disease (MRD) negativity rate.
To summarize the incidence, prevalence, and severity of adverse drug reactions according
to common terminology criteria for adverse events (CTCAE) NCI CTCAE version 5.0.
• To summarize the effect of this treatment combination on patients transitioning to
Hematopoietic stem cell transplant (HSCT) i.e., number and percentage of patients that
are able to proceed to HSCT.
To evaluate calaspargase pegol-mknl pharmacokinetics in relapsed refractory patients and
investigate its correlation with asparagine levels.
Exploratory Objectives:
To summarize associations between the genomic alterations in ALL (current biomarker
expression of the disease) with relation to the incidence of proceeding to HSCT in
patients with PR or stable disease (SD) after the induction cycle(s).
To evaluate the effect of anti-PEG and anti-ASP antibodies (PEG-ASP) on calaspargase
enzyme levels, and effect of calaspargase pegol-mknl pharmacokinetics on toxicities and
treatment outcomes.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Pediatric, adolescent, or young adult patients who have relapse or refractory T-cell
lymphoblastic leukemia (T-ALL) or T-Cell lymphoblastic lymphoma (T-LLy) according to
2017 WHO classification and NCCN v1 2021.
2. Patients have adequate performance status (ECOG ≤2) for patients≥16 years old,
Lansky score >50 for patients<16 years old.
3. Patients must be 1mo to 21 years of age at time of signing/or having proxy sign the
informed consent.
4. Patients with asymptomatic CNS disease are eligible (see also Exclusion Criterion #2
in section 4.2.)
5. The following conditions are allowed on study: conditions requiring systemic
glucocorticoid use, such as autoimmune disease, acute or chronic controlled graft
versus host disease (GVHD) or severe asthma. Patients are also allowed up to 5 days
of glucocorticoids as cytoreduction in combination with up to 3 doses of
cyclophosphamide (200 mg/m2/day) are allowed as standard pre-phase treatment up to 1
day before start of study treatment or cytarabine up to 2gm/m2. This can also be
discussed with PI.
6. Patients must have adequate organ function and laboratory results (obtained within
14 days of enrolment:
1. Total serum bilirubin ≤1.5 x upper limit of normal (ULN). Patients with known
Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN.
2. Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to
disease.
3. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x
ULN; ≤5 x ULN unless in case of suspected leukemic liver involvement
4. Amylase, Lipase and Triglycerides must be WNL prior to administration of
calaspargase pegol-mknl. If the lab values are outside the normal range, the
treating physicians can discuss dosing/enrolling per PI discretion.
7. Females of childbearing potential must have a negative serum or urine beta-human
chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the
first dose of study drugs and must agree to use one of the following effective
contraception methods during the study and for 3 months following the last dose of
study drug. Effective methods of birth control include:
1. Birth control pills, skin patches, birth control injections, implants (placed
under the skin by a health care provider)
2. Intrauterine devices (IUDs) and intra-uterine hormone-releasing systems (IUS)
3. Condom
4. Abstinence
5. Bilateral tubal occlusion/ligation or Bilateral tubal occlusion/ligation by
hysteroscopy with a hysterosalpingogram to confirm the procedure's success
8. Males need to inform the doctor right away if the partner becomes pregnant or
suspects pregnancy. While in this study and for 90 days after the last treatment the
patient should not donate sperm for the purposes of reproduction. He will need to
use a condom while in this study and for 90 days after the last treatment.
9. Patients must have had at least 30 days between prior hematopoietic stem cell
transplant and first dose of study drug.
10. Patients able and willing to swallow tablets or use oral dispersible tablets. No
liquid formulation is available.
Exclusion Criteria:
1. Past or current history of a secondary or other primary tumor or a chronic myeloid
leukemia (CML) blast crisis with exception of:
uratively treated non-melanomatous skin cancer, other primary solid tumor treated
with curative intent and no known active disease present, and no treatment
administered during the last 2 years
2. Presence of clinically significant uncontrolled CNS pathology such as epilepsy,
paresis, aphasia, stroke, severe brain injuries, organic brain syndrome, or
psychosis.
Presence of the following are allowed: headaches, vomiting, nerve palsy
3. Significant traumatic injury or major surgery (major surgery means opening of a body
cavity, e.g., thoracotomy, laparotomy, laparoscopic organ resection, and major
orthopedic procedures, e.g. joint replacement, open reduction, and internal
fixation) within 14 days of scheduled dosing day 1.
4. Male or female subjects of childbearing potential, unwilling to use an approved,
effective means of contraception in accordance with institution's standards.
5. Patients with uncontrolled infections (viral, bacterial, or fungal) per PI's
discretion. Infections controlled on concurrent anti-microbial agents are
acceptable, and anti-microbial prophylaxis per institutional guidelines are
acceptable.
6. Medical history of cardiovascular disease such as:
Clinically significant cardiac disease including congestive heart failure (NYHA
class III or IV), arrhythmia or conduction abnormality requiring medication, or
cardiomyopathy.
7. Female patient who is pregnant or breastfeeding. Female patient who is considering
becoming pregnant during the study; or within approximately 30 days after the last
dose of venetoclax, 3 months after the last dose of calaspargase or 6 months after
the last dose of decitabine. For decitabine and calaspargase, also see the study
drugs product label for pregnancy precautions. Male patient who is considering
fathering a child within approximately 30 days or donating sperm during the study,
within approximately 90 days after the last dose to venetoclax, calaspargase and
decitabine. For all study drugs, also see the relevant chemotherapy product label
for not fathering a child and donating sperm.
8. Patients may be excluded if they are currently enrolled in another ongoing clinical
trial with investigational products
9. Liver cirrhosis or other active severe liver disease or with suspected active
alcohol abuse.
10. Patients who are unable or unwilling to comply with all study requirements for
clinical visits, examinations, tests, and procedures.
11. If patient has not recovered from grade 2 clinically significant adverse
effect(s)/toxicity(s) of the previous therapy- (exception no grade 3 or higher
peripheral neuropathy) from previous chemotherapy, surgery, radiation before the
start of study drugs.
12. Pancreatitis: Patients will be excluded in the presence of Grade 3 or 4 pancreatitis
or if history of anaphylaxis or grade 3 pancreatitis from asparaginase.
13. Other severe, uncontrolled acute or chronic medical or psychiatric condition or
laboratory abnormality that in the opinion of the Investigator may increase the risk
associated with study participation or investigational product administration or may
interfere with the interpretation of study results and/or would make the patient
inappropriate for enrollment into this study.
14. History of serious hypersensitivity reactions including anaphylaxis to pegylated
L-Asparaginase therapy.
15. Known history of coagulopathy (e.g., hemophilia and know protein S deficiency).
16. Active thromboembolic event(s) (i.e., symptomatic despite initiation of
anti-coagulation therapy), or history of CNS thromboses.
17. Patients should not have received the following within 7days prior to the first dose
of study drug: Strong and moderate CYP3A inducers.
18. Malabsorption syndrome or any other condition that precludes enteral administration.
19. Has consumed grapefruit, grapefruit products, Seville oranges (including marmalade
containing Seville oranges) or Star fruit or used a strong or moderate CYP3A
inhibitor within 2 days prior to the first dose of venetoclax.
Gender:
All
Minimum age:
1 Month
Maximum age:
21 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77090
Country:
United States
Contact:
Last name:
David McCall, MD
Phone:
713-792-6604
Email:
dmccall1@mdanderson.org
Investigator:
Last name:
David McCall, MD
Email:
Principal Investigator
Start date:
February 28, 2025
Completion date:
December 31, 2031
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06561074
http://www.mdanderson.org
