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

This research study is a Phase I clinical trial, which tests the safety of an investigational
drug and also tries to define the appropriate dose of the investigational drug to use for
further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved ABI-009 as a treatment for
any disease.

The FDA has approved pomalidomide and dexamethasone as treatment options for multiple
myeloma.

The purpose of this study is to determine whether ABI-009 (study drug) will be safe and slow
the progress of the disease when used in combination with pomalidomide and dexamethasone,
depending on what type of cancer.

ABI-009 is an inhibitor of an overactive biological pathway in the cancer cells. Pomalidomide
is an immunomodulatory agent and believed to work by affecting the growth signals that keep
cancer cells alive. Dexamethasone is a steroid which is believed to kill cancer cells. The
investigators hope that the combination of ABI-009 with pomalidomide and dexamethasone will
help stop the growth of the cancer.

Inclusion Criteria:

- 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understanding that consent may be withdrawn by the subject at any time without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

- Patient has adequate hepatic function, as evidenced by the following:

- Serum bilirubin values < 2 mg/dL, and serum alanine transaminase (ALT), and serum
aspartate transaminase (AST) values < 3 × the institutional upper limit of normal
(ULN).

Patients with elevated bilirubin due to Gilbert's syndrome may be permitted with PI
approval

- Must be able to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation.
Patients intolerant to ASA may use low molecular weight heparin or equivalent.
Warfarin will be allowed provided patient is fully anticoagulated, with an INR of 2-3.

- All study participants must be registered into the mandatory POMALYST REMS program and
be willing and able to comply with the requirements of the POMALYST REMS program.

- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the POMALYST REMS program.

- Able to swallow capsules whole (pomalidomide capsules cannot be crushed, dissolved or
broken).

Exclusion Criteria:

- 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

- Hypersensitivity to thalidomide, lenalidomide, pomalidomide, bortezomib, or
dexamethasone (such as Stevens-Johnson syndrome). Rash to immunomodulatory drug that
can be medically managed is allowed

- Patients who had allogeneic stem cell transplant fewer than 12 months prior to
initiation of study treatment and who have not discontinued immunosuppressive
treatment for at least four weeks prior to initiation of study treatment and are
currently dependent on such treatment.

- Patients with active graft v. host disease.

- History of significant cardiovascular, neurological, endocrine, gastrointestinal,
respiratory, or inflammatory illness that could preclude study participation, pose an
undue medical hazard, or interfere with the interpretation of the study results,
including, but not limited to, patients with congestive heart failure (New York Heart
Association [NYHA] Class 3 or 4); unstable angina; cardiac arrhythmia; recent (within
the preceding 6 months) myocardial infarction or stroke; hypertension requiring > 2
medications for adequate control; diabetes mellitus with > 2 episodes of ketoacidosis
in the preceding 12 months; or chronic obstructive pulmonary disease (COPD) requiring
> 2 hospitalizations in the preceding 12 months.

- Patient has any other medical, psychiatric, or social condition that would preclude
participation in the study, pose an undue medical hazard, interfere with the conduct
of the study, or interfere with interpretation of the study results.

- History of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.

- Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving
the first dose of ABI-009. Additionally, use of any known CYP3A4 substrates with
narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride,
dihydroergotamine, pimozide, quinidine, terfanidine) within the 14 days prior to
receiving the first dose of ABI-009.