Study of Combination POM, BTZ, Low-Dose DEX, and DARA (PVD-DARA) in Patients With RRMM

NCT05408026 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: AFT-35
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II clinical trial design with a safety run-in period will be used to assess the rate of VGPR or better for the combination PVD-Dara in the treatment of RRMM.

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Safety Run-In Stage: Adverse events (AEs) will be assigned a grade and attribution using CTCAE v5.0 to determine the presence of dose-limiting toxicities (DLT).

  DLTs will be used to assess the safety profile \& determine tolerability of PVD-DARA in patients with RRMM. A DLT is the occurrence of any below toxicity during the first cycle probably, possibly or definitely related to study treatment: * Grade 4 neutropenia * Febrile neutropenia * Grade 4 thrombocytopenia * Grade 3 thrombocytopenia w/ bleeding * Grade 4 anemia, unexplained by underlying disease * Any non-hematological toxicity Grade ≥ 3, except: * Alopecia * Grade 3 nausea/vomiting/diarrhea for \< 72 hours w/ antiemetic \& other supportive care * Grade 3 fatigue for \< 1 week * Grade ≥ 3 isolated electrolyte abnormalities for ≤ 72 hours, not clinically complicated, resolve spontaneously/respond to conventional medical interventions * Grade ≥ 3 amylase/lipase elevation not associated w/ symptoms/clinical manifestations of pancreatitis * Grade 3 tumor lysis syndrome for ≤ 72 hours, not clinically complicated, resolves spontaneously/responds to conventional medical intervention

  4-9 months

• Phase II: To estimate the rate of Very Good Partial Response (VGPR) or better after 8 cycles of the combination PVD-DARA in patients with RRMM, including those with prior exposure to daratumumab

  To estimate the rate of VGPR or better after 8 cycles of the combination PVD-DARA in patients with RRMM, including those with prior exposure to daratumumab

  36 months

Secondary Outcomes (6)

• Rate of Adverse Events Grade ≥ 3 [Toxicity Profile]

  4 years

• Rate of Dose Omission [Toxicity Profile]

  4 years

• Rate of Dose Modification [Toxicity Profile]

  4 years

• To determine the overall response rate (ORR, including sCR, CR, VGPR, PR) after 8 cycles of the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab

  4 years

• To determine the Progression Free Survival (PFS) for the combination PVD-DARA in patients with RRMM, including patients previously exposed to daratumumab

  4 years

Study Arms (1)

Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab

EXPERIMENTAL

Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab

Drug: Daratumumab; Drug: Pomalidomide

Interventions

Daratumumab DRUG

Daratumumab (and hyaluronidase) will be given over 3-5 minutes subcutaneously (under the skin) in the clinic at alternating left/right abdominal sites. Patient will take dexamethasone orally (by mouth) either before coming to clinic or in clinic, before other medications. Only for the first cycle, patient will receive on Day 1 daratumumab (which is mixed with a compound called hyaluronidase) and dexamethasone, 1 day before patient start the other 2 medications.

Also known as: Dexamethasone

Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab

Pomalidomide DRUG

On day 2 of cycle 1, patient will start the other medications and will therefore receive bortezomib administered subcutaneously (SC) over 3-5 minutes and dexamethasone given orally (by mouth), either before coming to clinic or in clinic, before bortezomib. Patient will also start pomalidomide on the same day, which patient will take that evening at home and every evening for 21 days.

Also known as: Bortezomib

Combination of Pomalidomide, Bortezomib, Low-Dose Dexamethasone, and Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of symptomatic multiple myeloma.
• Evidence of disease progression or refractoriness to 1 to 3 prior lines of therapy by IMWG standard criteria.
• Prior exposure to lenalidomide and a proteasome inhibitor is mandatory.
• Daratumumab naïve patients or Daratumumab exposed patients who are not refractory to weekly or bi-weekly daratumumab.
• Measurable disease:
• Serum M protein ≥ 0.5 g/dL
• Urine M protein ≥ 200 mg/24 hours
• Involved serum free light chains ≥ 10 mg/dL AND an abnormal serum free light chain ratio
• ECOG Status 0-2 ≤ 14 days prior to registration
• Adequate organ function including ≤ 14 days prior to registration defined as:
• ANC ≥ 1.0 x 10\^9/L. (Patients cannot have received G-CSF or GM-CSF within 1 week of screening or pegfilgrastim within 2 weeks of screening)
• Platelets ≥ 75 x 10\^9/L
• Calculated Creatinine Clearance ≥ 30 mL/min
• Total Bilirubin ≤ 1.5 x ULN except for patients with a history of elevated total bilirubin, such as in Gilbert's
• AST, AP, ALT ≤ 3 x ULN

You may not qualify if:

• Disease refractory to weekly or bi-weekly daratumumab therapy.
• Female patients who are lactating or have a positive serum pregnancy test ≤ 14 days from registration during the screening period.
• Failure to have fully recovered from the reversible effects of prior anti-cancer therapy.
• Major surgery within 14 days before registration.
• Focal radiation therapy within 14 days prior to randomization with the exception of palliative radiotherapy for symptomatic management but not on measurable extramedullary plasmacytoma.
• Disease-related central nervous system involvement.
• Plasma cell leukemia, AL amyloidosis, or POEMS syndrome.
• The subject has uncontrolled significant intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled congestive heart failure, New York Heart Association Class III-IV, unstable angina pectoris, stroke, myocardial infarction, uncontrolled cardiac arrhythmias \< 6 months prior to registration, or uncontrolled hypertension.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
• Known GI disease or GI procedure that could interfere with the oral absorption of study medication including difficulty swallowing.
• Concurrent malignancy except for treated non-melanoma skin cancer, cervical carcinoma in situ and low-risk prostate CA being monitored without treatment.
• Grade 2 and higher peripheral neuropathy on clinical examination ≤ 14 days prior to registration.
• Chemotherapy ≤ 14 days prior to registration.
• Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.

Sponsors & Collaborators

• Alliance Foundation Trials, LLC.: lead
• Janssen, LP: collaborator
• Celgene: collaborator

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

daratumumab; Dexamethasone; pomalidomide; Bortezomib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2022
• First Posted: June 7, 2022
• Study Start: October 1, 2022
• Primary Completion: October 1, 2025
• Study Completion: February 1, 2026
• Last Updated: January 27, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share