Safety and Efficacy of ABI-009 (Nab-rapamycin) in Combination With Pomalidomide and Dexamethasone for Relapsed and Refractory Multiple Myeloma

NCT03657420 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 18-252
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying a combination of drugs as a possible treatment for multiple myeloma. The drugs that will be administered are:

• ABI-009 (nab-rapamycin)
• Pomalidomide
• Dexamethasone

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose.

  The maximum Tolerated Dose (MTD) is the highest dose of ABI-009 (nab-rapamycin) when administered in combination with pomalidomide and dexamethasone that dose not cause unacceptable side effects. The maximum tolerated dose is determined in clinical trials by testing increasing doses on different groups of people until the highest dose with acceptable side effects is found. A standard 3+3 dose escalation design will be used to assess the MTD.

  1 Cycle (28-Days)

Secondary Outcomes (3)

• Overall response rate.

  2 years

• Progression free survival.

  2 years

• Treatment-emergent adverse events.

  2 years

Study Arms (1)

ABI-009 + Pomalidomide + Dexamethasone

EXPERIMENTAL

* Pomalidomide is given orally daily on days 1-21, 7 days off * ABI-009 is given intravenously on days 1, 8, and 15 * Dexamethasone is given orally weekly on days 1, 8, 15, 22

Drug: ABI-009; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

ABI-009 DRUG

ABI-009 is an mTOR inhibitor. This pathway is believed to be overactive in multiple myeloma.

Also known as: nab-rapamycin

ABI-009 + Pomalidomide + Dexamethasone

Pomalidomide DRUG

Pomalidomide is an immunomodulatory agent and believed to work by affecting the growth signals that keep cancer cells alive.

Also known as: Pomalyst

ABI-009 + Pomalidomide + Dexamethasone

Dexamethasone DRUG

Dexamethasone is a steroid which is believed to kill cancer cells

Also known as: Decadron

ABI-009 + Pomalidomide + Dexamethasone

Eligibility Criteria

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

You may qualify if:

• Previously treated relapsed and refractory multiple myeloma. Relapsed and refractory is defined per International Myeloma Working Group Criteria (Rajkumar et al., 2011).
• Patients must have received at least two prior therapies with at least 2 cycles of lenalidomide and at least 2 cycles of a proteasome inhibitor (either in separate regimens or within the same regimen)
• Disease progression on or within 60 days of completion of last therapy.
• All laboratory assessments should be performed within 21 days of initiation of protocol therapy unless otherwise specified.
• Participant has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix A).
• Age ≥ 18 years
• Measurable disease of multiple myeloma as defined by at least one of the following:
• Serum monoclonal protein ≥ 0.5 g/dL
• ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum free light chain ≥ 100 mg/L (10 mg/dL) and abnormal serum free kappa to serum free kappa light chain ratio
• ANC ≥ 1000/μL. G-CSF is not permitted within 14 days of screening.
• Platelet count ≥ 75,000/µL. Platelet transfusions are not permitted within 7 days of screening.
• Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• Calculated creatinine clearance of ≥ 30 mL/min according to Cockroft-Gault equation

You may not qualify if:

• Prior therapy with mTOR inhibitor (e.g. everolimus, sirolimus). Note, prior pomalidomide therapy is permitted.
• Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Patients may have received dexamethasone within 2 weeks prior to entering study.
• Patients who are receiving any other investigational agents.
• Concomitant high dose corticosteroids except participants may be on chronic steroids (maximum dose 10 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, e.g. adrenal insufficiency, rheumatoid arthritis, etc.
• Pregnant or lactating females
• Prior history of malignancies, other than MM, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Ductal carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b)
• Patients undergoing active treatment for another malignancy with the exception of non-melanoma skin cancer or in situ cervical cancer.
• Patients with plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or amyloidosis are excluded from this trial.
• HIV infection
• Active hepatitis B infection or active hepatitis C infection, per treating investigator. Patients who have prior hepatitis C infection but who have received an antiviral treatment and show no detectable viral RNA for 6 months are eligible
• Peripheral neuropathy ≥ grade 2 despite supportive therapy

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Aadi Bioscience, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Andrew J. Yee, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 5, 2018
• Study Start: May 30, 2019
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2024
• Last Updated: August 14, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)