Gossypol Acetic Acid With Lenalidomide and Dexamethasone in Treating Patients With Relapsed Symptomatic Multiple Myeloma

NCT02697344 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: MC1384BNCI-2016-0007315-003501
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of R-(-)-gossypol acetic acid when given together with lenalidomide and dexamethasone and to see how well it works in treating patients with multiple myeloma, also known as plasma cell myeloma, that has come back after a period of improvement or has gotten worse after treatment. R-(-)-gossypol acetic acid may stop the growth of cancer cells by recognizing certain proteins and stimulating programmed cell death. Lenalidomide may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving R-(-)-gossypol acetic acid with lenalidomide and dexamethasone may work better in treating patients with multiple myeloma.

Conditions

Recurrent Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximally tolerated dose of AT-101 in combination with lenalidomide and dexamethasone defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (Phase I)

  The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The Grade 3+ adverse events will also be described and summarized in a similar fashion.

  Up to day 28 of course 2

• Overall response rate, with response defined to be a stringent complete response, complete response, very good partial response, or partial response (Phase II)

  Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 3 years

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 30 days after the last day of study drug treatment

• Overall survival (Phase II)

  Time from registration to death due to any cause, assessed up to 3 years

• Progression free survival (Phase II)

  Time from registration to the earliest date of documentation of disease progression or death due to any cause, assesse up to 3 years

Other Outcomes (6)

• Biochemical response, measured by change in serum/urine M-proteins and light chains

  Baseline to day 28 of course 1

• Change in basal expression of Bcl-2 and its family members

  Baseline to after completion of 2 courses of treatment (56 days)

• Change in basal expression pattern of protein kinase B (Akt), mitogen-activated protein kinase 1 (Erk), and mitogen-activated protein kinase (MAPK)

  Baseline to after completion of 2 courses of treatment (56 days)

Study Arms (1)

Treatment (AT-101, lenalidomide, and dexamethasone)

EXPERIMENTAL

Patients receive R-(-)-gossypol acetic acid PO QD on days 1-21. Beginning in course 2, patients also receive lenalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, and 15 of courses 2-12. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Other: Pharmacological Study; Drug: R-(-)-Gossypol Acetic Acid

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (AT-101, lenalidomide, and dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (AT-101, lenalidomide, and dexamethasone)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (AT-101, lenalidomide, and dexamethasone)

Pharmacological Study OTHER

Correlative studies

Treatment (AT-101, lenalidomide, and dexamethasone)

R-(-)-Gossypol Acetic Acid DRUG

Given PO

Also known as: (-)-Gossypol Acetic Acid, AT-101, GOSSYPOL ACETIC ACID, (R)-

Treatment (AT-101, lenalidomide, and dexamethasone)

Eligibility Criteria

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

You may qualify if:

• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 60 mL/min =\<14 days prior to registration
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 =\<14 days prior to registration
• Platelet count \>= 75000/mm\^3 =\<14 days prior to registration
• Hemoglobin \>= 8.0 g/dL =\<14 days prior to registration
• Patient must have relapsed and symptomatic multiple myeloma
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
• Serum monoclonal protein \>= 1.0 g/dL
• \>= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Patients must have received ≥3 prior regimens for multiple myeloma
• Provide informed written consent
• Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Arm A Only (Closed): Willing to provide bone marrow and blood samples for correlative research purposes

You may not qualify if:

• Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
• Patients who received daratumumab, pomalidomide and dexamethasone as the most immediate prior line of therapy prior to trial enrollment (prior therapy with a daratumumab-based or a pomalidomide-based regimen are allowed and prior daratumumab-pomalidomide-dexamethasone is allowed so long as it was not given as the most immediate prior line of therapy prior to trial enrollment).
• Other malignancy requiring active therapy EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (e.g., uncontrolled infection, uncompensated heart or lung disease)
• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Prior severe skin reaction (toxic epidermal necrosis) with immunomodulating agents
• Major surgery =\< 14 days before study registration
• Concurrent medical problems that preclude use of deep vein thrombosis (DVT) prophylaxis with lenalidomide treatment
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction =\< 6 months prior to registration
• Immunocompromised patients and patients known human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
• Uncontrolled intercurrent illness including, but not limited to

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide; gossypol acetic acid

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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sikander Ailawadhi, M.D.

  Mayo Clinic

  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: SPONSOR

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 3, 2016
• Study Start: April 14, 2016
• Primary Completion: October 26, 2018
• Study Completion: December 20, 2023
• Last Updated: December 28, 2023

Record last verified: 2023-12

Locations

US (1)