A Phase 2 Study of Venetoclax in Combination With Isatuximab and Dexamethasone for Relapsed/Refractory Multiple Myeloma Patients With t(11;14) VENETOCLAX PLUS ISATUXIMAB AND DEXAMETHASONE

What's the purpose of this trial?

A phase 2 study of venetoclax in combination with isatuximab and dexamethasone for relapsed/refractory multiple myeloma patients with t(11;14)

This is an upcoming trial that has not yet started accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

1. Have a diagnosis of MM based on standard criteria as follows, both criteria a and b must be met:

c. Clonal BM plasma cells ≥ 10% or biopsy-proven bony or extramedullary plasmacytoma

d. Any or more of the following myeloma defining events: i. Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

1. Hypercalcemia: serum calcium \>2.75 mmol/L (\>11 mg/dL) or \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal
2. Renal insufficiency: creatinine clearance \< 40mL/min or serum creatinine \> 177 mmol/L (\> 2mg/dL)
3. Anemia: hemoglobin value of \>2 g/dL below the lower limit of normal, or a hemoglobin value \<10 g/dL
4. Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT ii. Clonal BM plasma cell percentage \> 60% iii. Involved: uninvolved SFLC ratio \>100 (involved FLC level must be \>100 mg/L) iv. \> 1 focal lesion on MRI studies (at least 5 mm in size)

2. Show the t(11;14), confirmed by FISH or cytogenetic analysis , to be performed within 28 days prior to baseline. If performed more than 28 days prior, it should be repeated at the investigator's discretion

3. Absolute neutrophil count ≥ 1.5 x 10/L

4. Platelet count ≥ 75 x 109/L

5. Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment.

6. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute as calculated by Cockcroft-Gault method

7. Total bilirubin levels ≤ 2.0 mg/dL (normal levels)

8. AST (SGOT) and ALT (SGPT) ≤ 2 x ULN

9. Serum potassium within the normal range

10. Female of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking treatment drugs. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. Contraception measures should be continued for 3 months following the treatment completion.

* A FCBP (female of childbearing potential) is a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months

11. Eastern Cooperative Oncology Group (ECOG) performance score less than or equal to 2

12. Participant must have received at least 3 lines of prior treatment for MM, including regimens that contained a proteasome inhibitor, lenalidomide, and glucocorticosteroids

13. Participant currently has documented progressive MM per IMWG criteria

14. Subject must be ≥ 18 years of age

15. Subject must voluntarily sign and date an informed consent

Exclusion Criteria:

1. Participant has a history of intolerability to any of the study drugs
2. Participant has any of the following conditions: amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known human immunodeficiency viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of screening, or congestive heart failure New York Heart Association (NYHA) Class greater than or equal to 3, major surgery within 4 weeks prior to screening, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to screening, peripheral neuropathy greater than or equal to Grade 3 or greater than or equal to Grade 2 with pain within 2 weeks prior to screening, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to screening, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study
3. Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study
4. If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD)
5. Participants that are pregnant or breast feeding
6. Participants with hypersensitivity to any study medications and/or their excipients
7. Treatment with an anti-CD38 antibody (daratumumab or isatuximab) within the last six months
8. Treatment with an anti-CD38 antibody (daratumumab or isatuximab), alone or in combination, without achieving a best response of at least a MR
9. Treatment with venetoclax
10. Participants that are refractory to anti-CD38 antibody treatment \[i.e. disease progression (i.e., PD, per IMWG criteria) while receiving a CD38 MoAb or within 60 days of treatment (PD after 60 days after CD38 MoAb treatment is allowed)\]
11. Treatment with any of the following within 7 days prior to the first dose of study drug:

1. Steroid therapy for anti-neoplastic intent
2. Moderate or strong cytochrome P450 3A (CYP3A) inhibitors or inducers
12. Administration or consumption of any of the following within 3 days prior to the first dose of study drug:

d. Grapefruit or grapefruit products e. Seville oranges (including marmalade containing Seville oranges) f. Star fruit
13. Additional prior and concomitant therapy excluded and cautionary medications:

c. Excluded: i. Anticancer therapies including chemotherapy, radiotherapy, or other investigational therapy, including targeted small molecule agents: Excluded 5 half-lives prior to first dose and throughout venetoclax administration ii. Biologic agents (e.g., monoclonal antibodies) for anti-neoplastic intent: Excluded 28 days prior to first dose and throughout venetoclax administration

d. Cautionary during the study: i. Strong and Moderate CYP3A inhibitors: Exclude during ramp-up phase and consider alternative medications. If subject requires use of these medications at the cohort designated dose, use with caution and reduce the venetoclax dose by 50% for moderate inhibitors and at least 75% for strong inhibitors during co-administration. After discontinuation of CYP3A inhibitor, wait for 2 to 3 days before venetoclax dose is increased back to the initial maintenance/target dose.

ii. Strong and Moderate CYP3A inducers: Exclude during ramp-up phase and consider alternative medications. If subject requires use of these medications at the cohort designated dose, use with caution and contact AbbVie medical monitor for guidance.

iii. Additional: Warfarin, P-gp substrates, BCRP substrates, OATP1B1/1B3 substrates, P-gp inhibitors, BCRP inhibitors

Additional Trial Information

Phase 2

Enrollment: 39 patients (estimated)

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