Trial Title:
A Phase II Study of the Combination of Pembrolizumab and ATRA Combination Treatment of Relapsed HL and B-NHL
NCT ID:
NCT06484920
Condition:
Relapsed Hodgkin Lymphoma
Refractory Hodgkin Lymphoma
Relapsed Non-Hodgkin Lymphoma
Refractory Non-Hodgkin Lymphoma
B-cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ATRA
Description:
150 mg/m2 ATRA orally for 3 days surrounding each of the first four cycles (day -1, day
0, day +1)
Arm group label:
ATRA and Pembrolizumab
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
200mg Q3W pembrolizumab
Arm group label:
ATRA and Pembrolizumab
Summary:
This is a Phase II single-center open label trial of the combination of ATRA and
pembrolizumab treatment in patients with histologically proven, relapsed or refractory
Hodgkin Lymphoma or B-Non-Hodgkin-lymphoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. ≥ 18 years old at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization
3. Willingness to comply with all study procedures and be available for the duration of
the trial
4. Have a performance status of 0 to 2 on the ECOG Performance Scale.
5. Life expectancy ≥12 weeks as per investigator discretion
6. Patients with histologically proven, relapsed or refractory HL or B-NHL as follows:
1. HL after failure of at least 1 prior line of systemic therapy
2. Primary mediastinal large B-cell lymphoma (PMBCL) that is refractory to
first-line therapy
3. Other B-cell NHLs after failure of at least 2 prior lines of systemic therapy.
The eligible types of B-cell NHLs are:
i. Diffuse large B cell lymphoma ii. Follicular lymphoma iii. Marginal Zone lymphoma
iv. Mantle Cell Lymphoma d. Indolent lymphoma are only eligible if they require
systemic treatment e. Lymphocyte predominant HL are eligible Note: Formalin-fixed,
paraffin embedded archival tumor sample from the primary cancer must be available
for testing. If not available or sufficient, patients will be asked to undergo an US
or CT guided biopsy prior to study entry to satisfy this eligibility criterion.
7. Adequate hematologic and end organ function, defined by the following laboratory
results obtained within 10 days prior to the first study treatment: Hematological
Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9
g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of
assessment) INR and aPTT ≤1.5 x ULN; this applies only to patients who are not
receiving therapeutic anticoagulation; patients receiving therapeutic
anticoagulation should be on a stable dose. Renal calculated creatinine clearance
(GFR can also be used in place of creatinine or CrCl) calculated creatinine
clearance ≥ 60 mL/min Hepatic Serum total bilirubin
- 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels >
1.5 ULN (patients with known Gilbert disease who have bilirubin levels ≤ 3 x
ULN may be enrolled). Patients must be able to undergo biliary stenting if
required before or, if required, during the trial AST (SGOT) and ALT (SGPT) ≤
2.5 X ULN OR
- 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL
8. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. Note: Female of childbearing potential definition: (ECOG
definition) Any woman (regardless of sexual orientation, having undergone a tubal
ligation, or remaining celibate by choice) who meets the following criteria:
1. Has not undergone a hysterectomy or bilateral oophorectomy; or
2. Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 12 consecutive months).
9. Female subjects of childbearing potential must be willing to use an adequate method
of contraception for the course of the study through 120 days after the last dose of
study medication.
Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
Refer to section 8.4.1 for more information.
10. Male subjects of childbearing potential must agree to use an adequate method of
contraception of the protocol, starting with the first dose of study therapy through
120 days after the last dose of study therapy. Abstinence is acceptable if this is
the usual lifestyle and preferred contraception for the subject. Refer to section
8.4.1 for more information.
11. Acceptable methods of contraception include IUD, oral contraceptive, subdermal
implant, and double barrier (condom with a contraceptive sponge or contraceptive
pessary). Micro-dosed progesterone preparations ("mini-pill") are an inadequate
method of contraception during treatment with ATRA. If patients are taking this pill
they should be instructed to stop, and another form of contraceptive should be
prescribed instead.
12. Patients with a history of CAR-T cell therapy are eligible if ≥ 1 year post
treatment.
Exclusion Criteria:
1. Patients currently participating and receiving study therapy or has participated in
a study of an investigational agent and received study therapy or used an
investigational device within 4 weeks of the first dose of treatment.
2. Known brain metastases and/or leptomeningeal disease. Subjects with previously
treated brain metastases may participate provided they are radiologically stable,
i.e., without evidence of progression for at least 4 weeks by repeat imaging (repeat
imaging should be performed during study screening), clinically stable and without
requirement of steroid treatment for at least 14 days prior to first dose of study
treatment.
3. Significant reduction in ECOG performance status between the screening/ baseline
visit and within 72 hours prior to commencement of treatment as per trial protocol,
as per the Investigator's assessment, defined as a reduction in ECOG score to 3 or
4.
4. Patients with a diagnosis of immunodeficiency or receiving systemic steroid therapy
or any other form of immunosuppressive therapy (i.e., with use of disease modifying
agents, corticosteroids, or immunosuppressive drugs) within 7 days prior to the
first dose of trial treatment.
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered
a form of systemic treatment.
5. Hypersensitivity to pembrolizumab or any of its excipients.
6. Contraindication to the use of ATRA including but not limited to: patients with a
history of hypersensitivity reaction to tretinoin, vesanoid or related compounds (
i.e. acitretin, isotretinoin, vitamin A); , Tetracyclines, Progesterone (low dose),
drugs inducing P450 (rifampicin, glucocorticoids, phenobarbital, etc), ketoconazole
and drugs inhibiting p450 (cimetidine, erythromycin, cyclosporine, etc);
antifibrinolytic agents (e.g. tranexamic acid, aminocaproic acid, aprotinin) and
hydroxyurea)
7. Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day -1 or
who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to
agents administered more than 4 weeks earlier.
8. Prior chemotherapy targeted small molecule therapy, or radiation therapy within 2
weeks prior to study Day -1 or who have not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent. Subjects with
chronic conditions such as vision changes or prior hearing loss that is not
reasonably expected to be exacerbated by the investigational product may be
included. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this
criterion and may qualify for the study. Note: Subjects with Grade 2 adrenal
insufficiency or thyroid conditions who are not expected to resolve to baseline, are
on a stable dose of medication may be included if it is not reasonably expected to
be exacerbated by the investigational product, and asymptomatic whilst on treatment.
9. History of malignancy in the last 5 years with the exception of prior history of in
situ cancer or basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy, or in situ cervical cancer.
Patients with other malignancies are eligible if they were cured by surgery alone or
surgery plus radiotherapy and have been continuously disease-free for at least 5
years.
10. Patient has undergone major surgery, other than diagnostic surgery (i.e., surgery
done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks
prior to Day -1 of treatment in this study. Note: If subject received major surgery,
they must have recovered adequately from the toxicity and/or complications from the
intervention prior to starting therapy.
11. Known history of, or any evidence of active, non-infectious pneumonitis.
12. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic
therapy.
13. History or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
14. Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial.
15. Pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 120 days
after the last dose of trial treatment.
16. Patients on micro-dosed progesterone preparations ("mini-pill") who are unwilling to
receive an alternative form of contraception.
17. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
18. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
19. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
20. known history of active TB (Bacillus Tuberculosis).
21. Receipt of live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
22. Patients who receive a COVID shot and/or booster within 4 weeks of Cycle 1 Day -1.
23. Known sensitivity to retinoic acid derivatives.
24. Patient is taking any prohibited concurrent medication, including Vitamin A
supplements, and CYP3A modulators (inducers and inhibitors) and is unwilling to stop
use (washout period of 3 days for this protocol) prior to treatment start and during
the trial.
25. History of allogenic stem cell transplant or received a solid organ transplant.
Note: If history of transplant is ≥ 5 years, subjects may be deemed eligible at the
discretion of the treating physician. Note: Patients with a history of autologous
stem cell transplant performed for lymphoma are eligible.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Indiana University Health Melvin and Bren Simon Comprehensive Cancer Center
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelly White, RN
Phone:
317-278-5605
Email:
whitkell@iu.edu
Contact backup:
Last name:
Rita Assi, MD
Facility:
Name:
Sidney and Lois Eskenazi Hospital
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Hossam Elbanhawy
Phone:
317-278-6225
Email:
helbanha@iu.edu
Contact backup:
Last name:
Ahmad Al-Hader
Start date:
October 2024
Completion date:
September 2029
Lead sponsor:
Agency:
Rita Assi
Agency class:
Other
Source:
Indiana University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06484920
