We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Venetoclax, Daratumumab, and Dexamethasone for Systemic Light-Chain Amyloidosis With Translocation (11;14) (ALTITUDE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05486481
Recruitment Status : Not yet recruiting
First Posted : August 3, 2022
Last Update Posted : September 16, 2022
Sponsor:
Collaborators:
Janssen Pharmaceuticals
AbbVie
Information provided by (Responsible Party):
Sandy Wong, MD, University of California, San Francisco

Brief Summary:
This phase I/II trial tests the safety, side effects, and best dose of venetoclax, daratumumab, and dexamethasone for the treatment of systemic light-chain amyloidosis in patients with a deoxyribonucleic acid (DNA) abnormality called a translocation involving chromosomes 11 and 14, or "t(11;14)". Venetoclax works by attaching to a protein called Bcl-2, in order to kill cancer cells. Daratumumab works by binding to a target on the surface of cancer cells called CD38. When daratumumab binds to CD38, it enables the immune system to find the cancer cell and kill it. Dexamethasone is a type of drug called a corticosteroid. A corticosteroid is a drug made of artificial steroid hormones, that are used to treat symptoms such as inflammation (swelling and irritation to a part of the body). The combination of these medications may more effectively treat patients with systemic light-chain amyloidosis and t(11;14).

Condition or disease Intervention/treatment Phase
AL Amyloidosis Light Chain (AL) Amyloidosis Systemic Light Chain Disease Drug: Venetoclax Drug: Dexamethasone Drug: Daratumumab Phase 1 Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Non-randomized phase 1 dose-escalation enrollment will be followed by randomized, two-arm phase 2 enrollment.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase 1/2 Study of Venetoclax / Daratumumab / Dexamethasone for Previously Treated Systemic Light-Chain Amyloidosis Patients With Translocation (11;14) (ALTITUDE STUDY)
Estimated Study Start Date : January 15, 2023
Estimated Primary Completion Date : December 31, 2026
Estimated Study Completion Date : December 31, 2026


Arm Intervention/treatment
Experimental: Phase 1a: Dose Escalation Level 1 (venetoclax)
All patients receive 200 mg venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Venetoclax
Given orally (PO)
Other Name: Venclexta

Experimental: Phase 1a: Dose Escalation Level 2 (venetoclax)
All patients receive 400 mg venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Venetoclax
Given orally (PO)
Other Name: Venclexta

Experimental: Phase 1a: Dose Escalation Level 3 (venetoclax, dexamethasone)
All patients receive the maximum tolerated dose or the recommended phase 2 dose of venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle and, dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Venetoclax
Given orally (PO)
Other Name: Venclexta

Drug: Dexamethasone
Given PO
Other Name: Ozurdex

Experimental: Phase 1a: Dose Escalation Level 4 (venetoclax, dexamethasone, daratumumab)
All patients receive the maximum tolerated dose or the recommended phase 2 dose of venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle, dexamethasone PO on days 1, 8, 15, and 22 of each cycle, and daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, then on day 1 of cycles thereafter. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Venetoclax
Given orally (PO)
Other Name: Venclexta

Drug: Dexamethasone
Given PO
Other Name: Ozurdex

Drug: Daratumumab
Given Subcutaneously (SC)
Other Names:
  • Darzalex
  • Daratumumab SC

Experimental: Phase 1b: Dose Expansion (venetoclax, dexamethasone, daratumumab)
Phase 1b dose-expansion cohort will open if dose level 4 is the MTD/RP2D. All patients receive the maximum tolerated dose or the recommended phase 2 dose of venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle, dexamethasone PO on days 1, 8, 15, and 22 of each cycle with daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, then on day 1 of cycles thereafter. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Venetoclax
Given orally (PO)
Other Name: Venclexta

Drug: Dexamethasone
Given PO
Other Name: Ozurdex

Drug: Daratumumab
Given Subcutaneously (SC)
Other Names:
  • Darzalex
  • Daratumumab SC

Experimental: Phase 2: Arm A (venetoclax, dexamethasone, daratumumab)
Patients receive venetoclax PO QD on days 1-28 of each cycle, dexamethasone PO on days 1, 8, 15, and 22 of each cycle, and daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, then on day 1 of cycles thereafter. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity
Drug: Venetoclax
Given orally (PO)
Other Name: Venclexta

Drug: Dexamethasone
Given PO
Other Name: Ozurdex

Drug: Daratumumab
Given Subcutaneously (SC)
Other Names:
  • Darzalex
  • Daratumumab SC

Experimental: Phase 2: Arm B (dexamethasone, daratumumab)
Patients receive dexamethasone PO on days 1, 8, 15, and 22 of each cycle, and daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, then on day 1 of cycles thereafter. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Dexamethasone
Given PO
Other Name: Ozurdex

Drug: Daratumumab
Given Subcutaneously (SC)
Other Names:
  • Darzalex
  • Daratumumab SC




Primary Outcome Measures :
  1. Proportion of participants with reported dose limiting toxicities (Phase 1a) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]
    A dose limiting toxicity (DLT) will be defined as an adverse event that are considered by the investigator to be at least possibly related to the study drugs and are observed within the DLT assessment window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to extraneous causes.

  2. Maximum tolerated dose (MTD) (Phase 1a) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]
    The MTD is the last dose cohort at which no more than one instance of dose limiting toxicities (DLT) is observed among 6 participants treated. If the MTD cannot be determined due to lack of DLTs during the DLT window, the maximum dose level of venetoclax administered during the study will be declared the Recommended Phase 2 dose (RP2D).

  3. Recommended phase 2 dose (RP2D) (Phase1a) [ Time Frame: Up to 1 cycle (1 cycle is equal to 28 days) ]
    If the MTD cannot be determined due to lack of DLTs during the DLT window, the maximum dose level of venetoclax administered during the study will be declared the Recommended phase 2 dose (RP2D).

  4. Percentage of participants with treatment-emergent adverse events attributable to study treatment (Phase 1b/2) [ Time Frame: Up to 2 years ]
    Percentage of participants with reported treatment-emergent adverse events by type, severity, and attribution of probably, possible, or related to study drugs, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported.

  5. Proportion of participants who achieve a complete hematologic response (CHR) (Phase 2) [ Time Frame: Up to 2 years ]
    CHR is defined per updated 2021 International Society of Amyloidosis (ISA) consensus criteria as an absence of amyloidogenic light chains (either free and/or as part of a complete immunoglobulin) defined by negative immunofixation electrophoresis of both serum and urine, and also either a free-light chain (FLC) ratio within the reference range or the uninvolved FLC concentration is greater than involved FLC concentration with or without an abnormal FLC ratio. Patients with positive serum immunofixation (S-IFE) and confirmed daratumumab immunofixation (IFE) interference, that meet all other clinical criteria for CHR, will be considered CHR. CHR requires confirmation by 1 repeat assessment. Proportion and 95% binomial exact confidence interval will be reported


Secondary Outcome Measures :
  1. Percentage of participants with treatment-emergent adverse events attributable to study treatment (Phase 1a) [ Time Frame: Up to 2 years ]
    Percentage of participants with reported treatment-emergent adverse events by type, severity, and attribution of probably, possible, or related to study drugs, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be reported.

  2. Proportion of participants with complete hematologic response (CHR) (Phase 1b) [ Time Frame: Up to 2 years ]
    CHR is defined per updated 2021 International Society of Amyloidosis (ISA) consensus criteria as an absence of amyloidogenic light chains (either free and/or as part of a complete immunoglobulin) defined by negative immunofixation electrophoresis of both serum and urine, and also either a free-light chain (FLC) ratio within the reference range or the uninvolved FLC concentration is greater than involved FLC concentration with or without an abnormal FLC ratio. Patients with positive serum immunofixation (S-IFE) and confirmed daratumumab immunofixation (IFE) interference, that meet all other clinical criteria for CHR, will be considered CHR. CHR requires confirmation by 1 repeat assessment.

  3. Overall hematologic response rate (ORR) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    The proportion of participants enrolled in Phase 1b or either arm of Phase 2 who experience a hematologic objective response defined as a partial response (PR), a very good partial response (VGPR), or a complete response (CR) per updated 2021 ISA consensus criteria.

  4. Organ response rate (orRR) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    Organ disease considered to be quantifiable for response includes cardiac disease, renal disease, and hepatic disease. Liver organ response must be monitored by the ISA Consensus Criteria. Renal organ response must be monitored by Palladini criteria. Cardiac response must be monitored by the Boston University criteria. The proportion of participants enrolled in Phase 1b or either arm of Phase 2 who experience an organ response (Heart, kidney, and/or liver).

  5. Median Major Organ Deterioration Progression-Free Survival (MOD-PFS) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    MOD-PFS is defined as the time that elapses between initiation of trial therapy and the earlier of hematologic disease progression, cardiac deterioration that requires cardiac transplant, left ventricular assist device, or intra-aortic balloon pump, end-stage renal disease that requires hemodialysis or renal transplant, or death from any cause for participants enrolled in Phase 1b, or either arm of Phase 2. Median survival times will be reported in months along with 95% confidence intervals obtained using the Brookmeyer and Crowley (1982) method.

  6. Time to complete response (TTCR) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    TTCR is defined as the time that elapses between the initiation of trial therapy (C1D1) and the first time that complete hematological response (CHR) is recorded for participants enrolled in Phase 1b, or either arm of Phase 2.

  7. Median Time To Next Treatment (TTNT) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    For the RP2D combination, TTNT is defined as the time that elapses between the initiation of study treatment (C1D1) to the time the patient initiates subsequent anti-cancer therapy for participants enrolled in Phase 1b, or either arm of Phase 2. Median time will be reported in months along with 95% confidence intervals.

  8. Median Duration of response (DOR) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    DOR is defined as the time that elapses between the day of first documented hematological response to trial therapy (PR or better whichever is first recorded) to the date of first documented evidence of hematological disease progression participants enrolled in Phase 1b, or either arm of Phase 2. Median duration will be reported in months along with 95% confidence intervals.

  9. Median Progression-Free Survival (PFS) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    PFS is defined as the time that elapses between initiation of trial therapy and the earlier of the day of first documented disease progression (either hematologic or organ) or death from any cause for participants enrolled in Phase 1b, or either arm of Phase 2. Median survival times will be reported in months along with 95% confidence intervals obtained using the Brookmeyer and Crowley (1982) method.

  10. Median Overall Survival (OS) (Phase 1b/2) [ Time Frame: Up to 2 years ]
    The overall survival is defined as the time that elapses between the initiation of trial therapy (C1D1) and the date of death from any cause for all participants enrolled in either the Phase 1b arm, or either arm of Phase 2. Median survival times will be reported in months along with 95% confidence intervals obtained using the Brookmeyer and Crowley (1982) method.

  11. Overall number of participant deaths (Phase 2) [ Time Frame: Up to 2 years ]
    The number of participants enrolled in either arm of Phase 2 whose death occurred while the participant was on study will be reported.

  12. Number of treatment-related mortalities (Phase 2) [ Time Frame: Up to 2 years ]
    The number of participants enrolled in either arm of Phase 2 whose death was at least possibly attributable to treatment will be reported.

  13. Proportion of participants with infection (Phase 2) [ Time Frame: Up to 2 years ]
    The proportion of participants enrolled in either arm of Phase 2 who develop a documented infection will be reported.

  14. Percentage of participants with a cardiac event (Phase 2) [ Time Frame: Up to 2 years ]
    The percentage of participants enrolled in either arm of Phase 2 with a documented cardiac event will be reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >= 18 years
  • Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry (IHC) and polarizing light microscopy of green bi-refringent material in Congo red-stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance.

    *Considerations for specific populations where other types of amyloidosis may be encountered:

    • For male subjects 70 years of age or older who have cardiac involvement only, and patients of African descent (black subjects), mass spectrometry typing of AL amyloid in a tissue biopsy is recommended to rule out other types of amyloidosis such as age-related amyloidosis or hereditary amyloidosis (ATTR mutation)
  • Presence of t(11;14) on bone marrow plasma cells (BMPC) by fluorescence in-situ hybridization (FISH), performed at the University of California San Francisco (UCSF) cytogenetics laboratory
  • >= 1 prior line of therapy for the treatment of systemic AL amyloidosis. *Note: Induction with only autologous stem cell transplant is considered 1 line of therapy. Steroid monotherapy treatment will not be counted as 1 prior line of therapy per National Comprehensive Cancer Network (NCCN) guidelines. Patients are not required to having progressed from the prior line of therapy
  • No prior CD38-directed antibody treatment

    * or

    • If the patient previously received CD38-directed antibody treatment, the patient achieved >= partial response (PR) by amyloidosis consensus criteria and did not progress while on CD38-directed antibody therapy
    • Note: If the patient's last prior treatment included daratumumab and the patient relapsed (and does not meet the exclusion criteria as outlined in exclusion criterion #1) after cessation of treatment, a 3-month wash-out from CD38 antibody treatment is required. No washout period for DARA is deemed necessary when patients are already on DARA-based treatment and the treatment regimen needs to be stopped due to hematologic very good partial response (VGPR) or PR (suboptimal response) or non-DARA-related toxicity
  • Measurable disease of light chain amyloidosis as defined by at least ONE of the following:

    • Serum M-protein >= 0.5 g/dL by protein electrophoresis (routine serum protein electrophoresis and immunofixation (IFE) performed at a local laboratory),
    • Serum free light chain >= 40mg/L with an abnormal kappa:lambda ratio or
    • The difference between involved and uninvolved free light chains (dFLC) >= 20 mg/L
  • One or more organs impacted by AL amyloidosis according to consensus guidelines
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count >= 1.0 × 10^9/L without growth factor support for 7 days (14 days if pegfilgrastim) (within 1 day of cycle 1, day 1 [C1D1])
  • Hemoglobin level >= 8.0 g/dL (>= 5 mmol/L) (within 1 days of C1D1)
  • Platelet count >= 100 × 10^9/L without transfusion for 14 days (within 1 day of C1D1)
  • Alanine aminotransferase level (ALT) =< 2.5 times the upper limit of normal (ULN) (within 1 day of C1D1)
  • Aspartate aminotransferase (AST) =< 2.5 times the ULN (within 1 day of C1D1)
  • Total bilirubin level =< 3 × ULN except for subjects with Gilbert syndrome, in which case direct bilirubin =< 2 × ULN (within 1 day of C1D1)
  • Estimated glomerular filtration rate (eGFR) >= 20 mL/min/1.73 m^2 (within 1 day of C1D1)

    * Please note the eGFR is measured by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

  • Patients must have completed other systemic therapy >= 14 days or investigational drug/vaccine >= 28 days prior to treatment, focal radiation therapy >= 14 days, surgery (other than biopsies) >= 21 days prior to treatment, and any autologous stem cell transplant (ASCT) >= 100 days prior to start of treatment
  • Patients must not have received any medications or supplements which have been known to have some anti-amyloidogenic effect (such as: doxycycline; curcumin; prednisone; dexamethasone; epigallocatechin gallate) within 14 days prior to start of treatment
  • Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse (if this is the preferred and usual lifestyle of the subject) 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 4 weeks prior to treatment and continue for 30 days after discontinuation of venetoclax or 3 months after discontinuation of DARA SC, whichever is longer. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy
  • During the study and for 30 days after stopping VEN or 3 months after receiving the last dose of DARA SC, whichever is longer, a woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction
  • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control; e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository during and up to 30 days after discontinuation of VEN or 3 months after discontinuation DARA SC, whichever is longer. All men must also not donate sperm during the study and for 30 days after discontinuation of VEN or 3 months after discontinuation of DARA SC, whichever is longer
  • Patients must have documentation of yearly flu vaccination and a pneumococcus vaccination.

    * Note: If the patient is due for 2 doses of pneumococcus vaccination, patients must have documentation of having received one dose of vaccine. Live attenuated vaccines are not allowed

  • Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

  • Any prior hematologic progression to CD38 antibody therapy (regardless of presence of a response) while on treatment or within 90 days of the last dose.

    * Hematologic progression is defined as any ONE of the following:

    • From CR, any detectable monoclonal protein or abnormal free light chain ratio (the absolute concentration of the light chains must double)
    • From PR, 50% increase in serum M protein to >0.5 g/dl or 50% increase in urine M protein to 4200 mg/day (a visible peak must be present)
    • Free light chain increase of 50% to >100 mg/l
  • Prior exposure to venetoclax
  • Intolerance to anti-CD38 antibody therapy, monoclonal antibodies, or hyaluronidase
  • Previous or current diagnosis of multiple myeloma by International Myeloma Working Group (IMWG) criteria, including the presence of lytic bone disease, plasmacytomas, >= 60% plasma cells in the bone marrow, or hypercalcemia
  • Systemic AL amyloidosis from a lymphoma
  • Any form of non-AL amyloidosis, including wild type or mutated (ATTR) amyloidosis
  • Evidence of significant cardiovascular conditions as specified below:

    • Troponin I >0.1 ng/ml and B-type natriuretic peptide (BNP) >700 pg/ml (cardiac stage 3B)
    • Left ventricular ejection fraction (LVEF) <40%
    • New York Heart Association (NYHA) classification IIIB or IV heart failure
    • Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (e.g. prior myocardial infarction with documented history of cardiac enzyme elevation and electrocardiogram [ECG] changes) or uncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy
    • Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months
    • For patients with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to randomization
    • Patients with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker/implantable cardioverter-defibrillator (ICD) is indicated but not placed

      ** Note: Patients who do have a pacemaker/ICD are allowed on study

    • Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >500 msec

      ** Note: Patients who have a pacemaker may be included regardless of calculated QTc interval

    • Supine systolic blood pressure <90 mm Hg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of >20 mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absence of volume depletion
  • Planned stem cell transplant

    * Note: Stem cell collection is permitted. Timing should be discussed with sponsor-investigator

  • History of malignancy (other than AL amyloidosis) within 3 years before the date of study enrollment

    * Note: Exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)

  • For patients with known or suspected COPD, chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal are excluded

    *Note: FEV1 testing is required only for patients known or suspected of having COPD and patients must be excluded if FEV1 is < 50% of predicted normal

  • Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification

    * Note: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate

  • Participant meets one of the following criteria:

    • Known history of human immunodeficiency virus (HIV)
    • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg])

      ** Note: Patients with resolved infection (i.e., patients who are HBsAg negative with antibodies to total hepatitis B core antigen (anti-HBc) with or without the presence of hepatitis B surface antibody (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. However, patients with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination, do not need to be testing for HBV DNA by PCR, and will not be excluded.

    • 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)
  • 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
  • Has not recovered from adverse events due to prior anti-cancer therapy to <= grade 1 or baseline (other than alopecia)
  • Systemic treatment with any of the following within 7 days prior to the first dose of study drug:

    • Steroid therapy for anti-neoplastic intent
    • Known moderate or strong cytochrome P450 3A (CYP3A) inhibitors
    • Known moderate or strong CYP3A inducers ** Note: Patients who are taking strong CYP3A4 inducers must discontinue their use at least 5 half-lives prior to the first dose of study treatment
  • Administration or consumption of any of the following within 3 days prior to the first dose of study drug:

    • Grapefruit or grapefruit products
    • Seville oranges (including marmalade containing Seville oranges)
    • Starfruit
  • Patient anticipates use of prohibited medications or foods during study participation
  • Major surgery within 2 weeks before Cycle 1 Day 1, or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study treatment administration

    * Note: Patients with planned surgical procedures to be conducted under local anesthesia may participate

  • Known or suspected of not being able to comply with the study protocol or the patient has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient (e.g., compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments
  • Woman who is pregnant or breastfeeding or planning to become pregnant while enrolled in this study or within 3 months following discontinuation of daratumumab or venetoclax
  • Have received vaccination with live attenuated vaccines within 4 weeks of first study agent administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05486481


Contacts
Layout table for location contacts
Contact: Laurel Brechtel (415) 502-1564 laurel.brechtel@ucsf.edu

Locations
Layout table for location information
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Contact: Laurel Brechtel    415-502-1564    Laurel.Brechtel@ucsf.edu   
Contact    877-827-3222    cancertrials@ucsf.edu   
Principal Investigator: Sandy W Wong, MD         
Sponsors and Collaborators
Sandy Wong, MD
Janssen Pharmaceuticals
AbbVie
Investigators
Layout table for investigator information
Principal Investigator: Sandy W Wong, MD University of California, San Francisco
Layout table for additonal information
Responsible Party: Sandy Wong, MD, Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT05486481    
Other Study ID Numbers: 22253
NCI-2022-05530 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
First Posted: August 3, 2022    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sandy Wong, MD, University of California, San Francisco:
Translocation
Additional relevant MeSH terms:
Layout table for MeSH terms
Immunoglobulin Light-chain Amyloidosis
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Paraproteinemias
Dexamethasone
Venetoclax
Daratumumab
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors