R-(-)-Gossypol Acetic Acid With Lenalidomide and Dexamethasone in Treating Patients With Relapsed Symptomatic Multiple Myeloma



Status:Suspended
Conditions:Hematology, Hematology
Therapuetic Areas:Hematology
Healthy:No
Age Range:18 - Any
Updated:11/2/2018
Start Date:April 14, 2017
End Date:June 15, 2021

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Phase 1/2 Trial of AT-101 in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Symptomatic Multiple Myeloma

This phase I/II 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.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of R-(-)-gossypol acetic acid (AT-101) that can be
combined with lenalidomide and dexamethasone in patients with relapsed symptomatic multiple
myeloma (MM). (Phase I) II. To determine the overall response rate (partial response or
better) of AT-101 when used in combination with lenalidomide and dexamethasone in patients
with relapsed symptomatic MM. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the progression free survival and overall survival among patients with
relapsed symptomatic MM following treatment with AT-101 in combination with lenalidomide and
dexamethasone.

II. To determine the toxicities associated with AT-101 in combination with lenalidomide and
dexamethasone in patients with relapsed symptomatic MM.

TERTIARY OBJECTIVES:

I. Determine in vivo the anti-myeloma effect of AT-101 alone by assessing extent of decrease
in M-protein (serum and/or urine) after 1 cycle of AT-101 alone.

II. Determine the pharmacodynamics effect of AT-101 in combination with lenalidomide and
dexamethasone treatment on primary myeloma cell in vivo.

III. Explore potential mechanism of resistance to AT-101 in combination with lenalidomide and
dexamethasone therapy and the role of B-cell CLL/lymphoma 2 (Bcl-2).

OUTLINE: This is a phase I dose-escalation study of R-(-)-gossypol acetic acid followed by a
phase II study.

Patients receive R-(-)-gossypol acetic acid orally (PO) once a day (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. Treatment repeats every 28 days for 12 courses in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 3 years.

Inclusion Criteria:

- Calculated creatinine clearance (using Cockcroft-Gault equation) >= 60 mL/min

- Absolute neutrophil count (ANC) >= 1000/mm^3

- Platelet count >= 75000/mm^3

- Hemoglobin >= 8.0 g/dL

- 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 at least 1 prior regimen

- 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)

- Willing to provide bone marrow and blood samples for correlative research purposes

Exclusion Criteria:

- Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma

- Patients who have received > 3 prior treatment regimens for multiple myeloma

- 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:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception

- Other co-morbidity which would interfere with patient's ability to participate in
trial, 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

- Known human immunodeficiency virus (HIV) positive

- 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
We found this trial at
1
site
4500 San Pablo Rd S
Jacksonville, Florida 32224
(904) 953-2000
Principal Investigator: Asher A. Chanan-Khan
Phone: 855-776-0015
Mayo Clinic Florida Thousands of people come to Mayo Clinic in Jacksonville, Fla., annually for...
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