Study Drug Administration:
Each cycle is 28 days.
If participant is found to be eligible to take part in this study, participant will receive
daratumumab by vein over about 4 hours on Days 1, 8, 15, and 22 of Cycles 1 and 2, Days 1 and
15 of Cycles 3-6, and then on Day 1 of Cycles 7 and beyond. Participant's first dose of
daratumumab will be given over about 7 hours.
In this study, the following will be done to lower the chance of a daratumumab infusion
related reaction:
- Participant will get medications, including steroids, acetaminophen, and/or
antihistamine before the infusion. If participant is considered high risk, participant
may also get medications, including inhaled steroids, after the infusion.
- The infusion may be slowed down or stopped if participant has a reaction.
- Participant may stay overnight in the hospital after the infusion so the study staff can
check participant's health.
Participant may ask the study staff for information about how these drugs are given and their
risks. Participant may also be asked to stay in the hospital overnight to watch participant
for side effects, if needed.
Length of Study:
Participant may receive daratumumab for up to 1 year. Participant will no longer be able to
take the study drug if the disease gets worse, if intolerable side effects occur, or if
participant is unable to follow study directions.
Study Visits:
Within 24 hours before participant's first dose of study drug, if participant can become
pregnant, blood (about 1 teaspoon) will be drawn for a pregnancy test.
Every 2 weeks during Cycles 1-6, blood (about 1 teaspoon) will be drawn for CMV testing.
On Day 1 of Cycles 1 and 2:
- Participant will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- Blood (about 2 teaspoons) will be drawn for pharmacokinetic (PK) testing before
participant's dose of study drug. Blood (about 1 teaspoon) for PK testing will also be
drawn 2 times over the 2 hours after the dose. During Cycle 2, blood will only be drawn
1 time after the dose. PK testing measures the amount of study drug in the body at
different time points.
- During Cycle 1, blood (about 1 teaspoon) will be drawn for immune system testing.
- During Cycle 2, participant will have a bone marrow aspirate/biopsy to check the status
of the disease.
On Days 2 and 4 of Cycle 1, blood (about 1 teaspoon) will be drawn for PK testing.
On Days 8, 15, 22 of Cycles 1 and 2, blood (about 2 teaspoons) will be drawn for routine
tests. On Day 8 of Cycle 1, blood (about 1 teaspoon) will be drawn before participant's dose
of study drug for PK testing.
Day 22 of Cycle 2, blood (about 1 teaspoon) will be drawn for PK testing before and after
participant's dose of study drug.
On Day 1 of Cycles 3-6:
- Participant will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- During Cycle 3, participant will have an EKG.
- During Cycle 3, blood (about 1 teaspoon each time) will be drawn for PK testing before
and after participant's dose of study drug.
- If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a
pregnancy test.
On Day 1 of Cycles 3 and beyond, participant will have a bone marrow biopsy/aspirate to check
the status of the disease. If the disease appears to be responding to the study drug, the
study doctor will decide how often participant will have this procedure.
On Day 15 of Cycles 3-6, blood (about 2 teaspoons) will be drawn for routine tests.
On Day 1 of Cycles 7 and beyond:
- Participant will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests and CMV testing.
- During Cycle 7 only, participant will have an EKG.
- During Cycles 7 and 12, blood (about 2 teaspoons) will be drawn for PK and immune system
testing.
- If participant can become pregnant, blood (about 1 teaspoon) will be drawn for a
pregnancy test.
While on study, if participant chooses to not have any of the PK blood draws, participation
in this study will be over.
End of Treatment:
About 28-35 days after the last dose of daratumumab:
- Participant will have a physical exam.
- Participant will have an EKG.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- If the doctor thinks it is needed, participant may have a bone marrow biopsy/aspiration
to check the status of the disease.
Follow-Up Visits:
The study staff will call participant to ask how participant is doing 1 time each month for
the first year after participant's End-of-Treatment visit, then every 6 months during the
second year after the visit, and then 1 time every year after that. Each call should last
about 5 minutes.
At 4 and 8 weeks after participant's last dose of study drug, blood (about 2 teaspoons) will
be drawn for PK and immune system testing.
At 30 and 60 days after participant's last dose of study drug and then every 2-3 months after
that for 1 year:
- Participant will have a physical exam.
- If the disease appeared to be responding to the study drug, blood (about 2 teaspoons)
will be drawn for routine tests. Every 4-12 weeks, this sample may be used for CMV
testing. If the disease appears to get worse, participant will stop having these blood
draws.
- If the disease appeared to be responding to the study drug, participant will have a bone
marrow aspirate and/or biopsy.
- If the disease appeared to be responding to the study drug, participant will have an EKG
at participant's first follow-up visit.
After 1 year, participant may continue to have follow-up visits as part of participant's
routine care. This will be discussed with participant by the study doctor in more detail.
This is an investigational study. Daratumumab is FDA approved and commercially available for
treatment of multiple myeloma. It is considered investigational to use daratumumab to treat
ALL.
The study doctor can explain how the study drug is designed to work.
Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.
Inclusion Criteria:
1. Subject must be at least 18 years of age.
2. The subject must have precursor B-cell or T-cell acute lymphoblastic leukemia. B-cell:
relapsed or refractory after first or subsequent salvage therapy; or T-cell: relapsed
or refractory with first remission duration less than or equal to 12 months in first
salvage; or relapsed or refractory after first or subsequent salvage therapy.
3. More than 5% blasts in bone marrow.
4. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
5. Life expectancy of >/= 12 weeks.
6. Women of childbearing potential must commit to either abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control
simultaneously. This includes one highly effective form 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 prior to dosing. Reliable contraception is indicated
even where there has been a history of infertility, unless due to hysterectomy or
bilateral oophorectomy. A man who is sexually active with a woman of childbearing
potential must always use a latex or synthetic condom during the study and for 4
months after discontinuing daratumumab.
7. A woman of childbearing potential must have a negative serum or urine pregnancy test
at screening within 14 days and again within 72 hours prior to dosing.
8. Each subject must sign an informed consent form (ICF) indicating that he or she
understands the purpose of and procedures required for the study and are willing to
participate in the study. Subjects must be willing and able to adhere to the
prohibitions and restrictions specified in this protocol, as referenced in the ICF.
Exclusion Criteria:
1. Active leukemic central nervous system (CNS) disease.
2. Active acute Graft-versus-Host Disease (GvHD) or chronic GVHD grade 2 or higher.
3. Patients who have received prior stem cell transplantation will be allowed to enroll
as long as prior transplantation has been at least 3 months before enrollment in the
trial and any transplant related toxicities have subsided to Grade 1 or less.
4. Philadelphia chromosome-positive (Ph+) ALL.
5. Cancer chemotherapy within 2 weeks prior to start of daratumumab treatment (steroid or
hydroxyurea can be used up to 24 hours prior to first daratumumab infusion for control
of high white cell counts)
6. Cancer immunotherapy within four weeks prior to start of daratumumab treatment
(exception blinatumomab within two weeks prior)
7. Diagnosed or treated for malignancy other than ALL, except: 1) Malignancy treated with
curative intent and with no known active disease present for >/= 3 years before
treatment; 2) Adequately treated non-melanoma skin cancer or lentigo maligna or
carcinoma in situ (e.g. cervical, breast) without evidence of disease; 3) or
malignancy that in the opinion of the investigator, with concurrence with the MDACC
IND office, is considered cured with minimal risk of recurrence within 3 years.
8. Subject has known chronic obstructive pulmonary disease (COPD) with a Forced
Expiratory Volume in 1 second (FEV1) <50% of predicted normal. NOTE: FEV1 testing is
required for patients suspected of having COPD and subjects must be excluded if FEV1
<50% of predicted normal.
9. Subject has known moderate or severe persistent asthma within the past 2 years (see
Appendix A: Classification of Asthma Severity), or currently has uncontrolled asthma
of any classification. NOTE: subjects who currently have controlled intermittent
asthma or controlled mild persistent asthma are allowed in the study.
10. Subject is known to be seropositive for human immunodeficiency virus (HIV), hepatitis
B surface antigen, or hepatitis C antibody (unless treated curatively).
11. Subject has any concurrent medical condition or disease (e.g, active systemic
infection) that is likely to interfere with study procedures or results, or that in
the opinion of the investigator would constitute a hazard for participating in this
study.
12. Subject has any of the following laboratory test results at cycle 1 day 1 pre-dosing:
1) Alanine aminotransferase level (ALT) >/= 2.5 x the upper limit of normal (ULN); 2)
Aspartate Aminotransferase (AST) >/= 2.5 x the ULN; 3) Total bilirubin level >/= 1.5 x
ULN, (except for Gilbert Syndrome: direct bilirubin >/= 1.5 x ULN); 4) Creatinine > 2
x ULN.
13. Subject has clinically significant cardiac disease, including: 1) myocardial
infarction within 1 year before study enrollment, or an unstable or uncontrolled
disease/condition related to or affecting cardiac function (e.g., unstable angina,
congestive heart failure, New York Heart Association Class III-IV); 2)uncontrolled
cardiac arrhythmia or clinically significant ECG abnormalities; 3) screening 12-lead
ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470
msec.
14. Subject has known allergies, hypersensitivity, or intolerance to boron or mannitol,
corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer
to respective package inserts or Investigator's Brochure), or known sensitivity to
mammalian-derived products.
15. Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant
while enrolled in this study or within 4 months after the last dose of any component
of the treatment regimen. Or, subject is a man who plans to father a child while
enrolled in this study or within 4 months after the last dose of any component of the
treatment regimen.
