Trial Title:
A Phase I Study of Hyper-CVAD In Combination With Venetoclax In Pediatric Patients With Relapsed or Refractory Acute Leukemias That Are of the Lymphoid Lineage Including Bi-Phenotypic or Undifferentiated Leukemias
NCT ID:
NCT06466395
Condition:
Refractory Acute Leukemia
Relapsed Acute Leukemia
Undifferentiated Leukemia
Bi-Phenotypic Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid, Acute
Acute Disease
Venetoclax
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given by PO
Arm group label:
Phase 1a
Arm group label:
Phase 1b
Other name:
ABT-199
Other name:
GDC-0199
Intervention type:
Drug
Intervention name:
Hyper-CVAD
Description:
Given by IV
Arm group label:
Phase 1a
Arm group label:
Phase 1b
Summary:
To find the recommended dose of hyper-CVAD in combination with venetoclax that can be
given to participants with relapsed or refractory leukemia.
Detailed description:
Primary Objectives
- To determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose
(RP2D) of venetoclax in combination with hyper-CVAD in patients with relapsed or
refractory acute leukemias that are of the lymphoid lineage including bi-phenotypic
or undifferentiated leukemias.
- To characterize the safety and tolerability of hyper-CVAD in combination with
venetoclax.
Secondary Objectives
- To determine the preliminary assessment of efficacy by overall response (OR),
including complete remission (CR), CR with incomplete blood count recovery (CRi) and
partial response (PR).
- Evaluate additional measures of clinical benefit including overall survival (OS),
event-free survival (EFS), progression-free survival (PFS) minimal residual disease
(MRD) rate, and duration of response (DOR).
Exploratory Objectives
. To evaluate the pharmacodynamics (PD) and biological effects of hyper-CVAD in
combination with venetoclax through molecular and cellular markers that may be predictive
of antitumor activity and/or resistance.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Relapsed/refractory leukemias as defined as:
1. Pediatric, adolescent, or young adult patients with relapsed or refractory
acute leukemias that are of the lymphoid lineage including bi-phenotypic or
undifferentiated leukemias as per NCCN v2.2021 and W.H.O. classification in
relapse or primary refractory.
2. Participants must have ≥5% blasts in the bone marrow as assessed by morphology.
However, if an adequate bone marrow sample cannot be obtained, patients may be
enrolled if there is unequivocal evidence of leukemia with ≥5% blasts in the
peripheral blood.
2. Participants have adequate performance status (ECOG ≤2) for patients ≥16 years old,
Lansky score >50 for patients <16 years old.
3. Participants must be ≥ 2 years old or less than or equal to 21 years of age at time
of signing/or having proxy sign the informed consent to be enrolled on study.
4. Participants with asymptomatic CNS disease are eligible.
5. These conditions are allowed on study: conditions requiring chronic systemic
glucocorticoid use, such as autoimmune disease, graft versus host disease (GVHD)
(well controlled on a stable dose of steroid or alternative therapy) or severe
asthma. Participants are also allowed up to 5 days of glucocorticoids as
cytoreduction, the use of hydroxyurea and the usage of cytarabine up to 2gm/m2. This
should also be discussed with PI.
1. For participants on chronic glucocorticoid therapy: Participants should be on
stable systemic steroid doses less than or equal to 11.6mg/m2 (20 mg max) of
prednisone daily
- During times of dexamethasone dosing (cycles 1,3,5 and 7): Hold chronic
steroids on days dexamethasone is given then resume normally scheduled
chronic steroid dosing the following day.
- Participants on chronic steroids > 11.6mg/m2 (20 mg max) prednisone
equivalent will be excluded from the study.
2. The use of topical steroids for cutaneous graft-versus-host disease (GVHD) is
allowed.
3. Participants should be at least 2 weeks or 5 half-lives (whichever is longer)
from prior therapy, other than hydroxyurea, glucocorticoids or low dose
cytarabine (as mentioned above) to maintain blast count prior to initiation of
study therapy.
6. Participants must have adequate organ function and laboratory results (obtained
within 14 days of enrollment):
6.1. Total serum bilirubin ≤1.5 x upper limit of normal (ULN). Participants with
known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN.
6.2. Adequate renal function (creatinine clearance >30mL/min) unless related to the
disease.
6.3. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x
ULN; ≤5 x ULN unless in case of suspected leukemic liver involvement Females of
childbearing potential must have a negative serum or urine beta-human chorionic
gonadotropin (beta-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.
The effects of these investigational agents on the developing human fetus are
unknown. For this reason and because chemotherapeutic and inhibiting agents as well
as other therapeutic agents used in this trial are known to be teratogenic, women of
child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. This includes all female patients, between the
onset of menses (as early as 8 years of age) and 55 years unless the patient
presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months).
- History of hysterectomy or bilateral salpingo-oophorectomy.
- Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal
range, who have received Whole Pelvic Radiation Therapy).
- History of bilateral tubal ligation or another surgical sterilization
procedure.
- Approved methods of birth control are as follows: Hormonal contraception
(i.e. birth control pills, injection, implant, transdermal patch, vaginal
ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy,
Subject/Partner post vasectomy, Implantable or injectable contraceptives,
and condoms plus spermicide. Not engaging in sexual activity for the total
duration of the trial and the drug washout period is an acceptable
practice; however periodic abstinence, the rhythm method, and the
withdrawal method are not acceptable methods of birth control. Should a
woman become pregnant or suspect she is pregnant while she or her partner
is participating in this study, she should inform her treating physician
immediately.
7. Males need to inform the doctor right away if the partner becomes pregnant or
suspects pregnancy. While in this study and for 30 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 30 days after the last treatment.
8. Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 4
months after completion of all study drug administration. Participants must have had
at least 30 days between prior hematopoietic stem cell transplant and first dose of
study drug.
9. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
10. Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For participants with HCV infection who are currently on
treatment, they are eligible if they have an undetectable HCV viral load.
11. Ability to understand and the willingness to sign a written informed consent
document.
12. Participants with CD19+ B-ALL need to have received CD19-directed therapy prior to
being considered for enrollment on this study.
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:
- curatively 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. Participants 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.
5. Medical history of cardiovascular disease such as:
Clinically significant cardiac disease defined as congestive heart failure (NYHA
class III or IV), arrhythmia or conduction abnormality requiring medication, or
cardiomyopathy. This will be reviewed during screening EKG/ECHO as well as prior
documentation.
6. Females who are pregnant or lactating.
7. Participants may be excluded if they are currently enrolled in another ongoing
clinical trial with investigational products.
8. Liver cirrhosis or other active severe liver disease or with suspected active
alcohol abuse.
9. Participants who are unable or unwilling to comply with all study requirements for
clinical visits, examinations, tests, and procedures.
10. If participant has not recovered from previous chemotherapy, surgery, radiation
before the start of study drugs.
11. 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.
12. Participants with active/uncontrolled HIV infection, AIDS, or currently taking
contraindicated medications for HIV control
13. History of allergic reactions attributed to compounds of similar chemical or
biologic composition to all agents used in study. Since each reaction can vary from
mild pruritis to anaphylaxis, the reaction will be discussed with PI prior to
excluding participant.
Gender:
All
Minimum age:
2 Years
Maximum age:
21 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
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:
December 31, 2024
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/NCT06466395
http://www.mdanderson.org
