Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

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Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Recurrence

Smoldering Multiple Myeloma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Precancerous Conditions

Hypergammaglobulinemia

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

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All Drugs and Chemicals

Dexamethasone

Melphalan

Bortezomib

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Patients receive melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also receive dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients undergo autologous hematopoietic stem cell transplant. Eligible patients may undergo a second transplant 2-4 months after completion of the first transplant.

Undergo autologous hematopoietic stem cell transplant

Autologous Transplant

Choon-Kee Lee, MD

This phase I/II trial studies the safety and best dose of melphalan and bortezomib when given prior to an autologous stem cell transplant and to see how well they work in treating patients with multiple myeloma. Drugs used in chemotherapy, such as melphalan, 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. Bortezomib may help melphalan work better by making cancer cells more sensitive to the drug. Giving chemotherapy before an autologous hematopoietic stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving melphalan together with bortezomib prior to autologous hematopoietic stem cell transplant may be a better treatment for multiple myeloma.

This is a phase I, dose-escalation study of melphalan and bortezomib followed by a phase II study.

Patients receive melphalan intravenously (IV) continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also receive dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients undergo autologous hematopoietic stem cell transplant. Eligible patients may undergo a second transplant 2-4 months after completion of the first transplant.

After completion of study treatment, patients are followed up monthly for at least 1 year and then every 3-6 months thereafter.

Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma

A Phase I-II Study of Infusional Melphalan + Bortezomib for Myeloablative Therapy Prior to Autologous Transplant for Patients With Multiple Myeloma

MTD is defined as one dose below that which 33% of patients within cohort experienced dose limiting toxicity. Unacceptable toxicity is defined as intractable veno-occlusive disorder, new onset of renal failure requiring dialysis, acute heart failure of New York Heart Association class III/IV, or interstitial pneumonia requiring ventilator management for longer than 3 days or grade 4 neuropathy. A 100-day mortality/toxicity rate of 3% or more is considered unacceptable. Will consider as evidence an observed 100-day mortality/toxicity rate whose lower one-sided 90% confidence bound exceeds 3%.

University of Colorado, Denver

Patients received melphalan IV continuously on days -5 to -2 and bortezomib IV over 3-5 seconds on days -4 and -1. Patients also received dexamethasone IV on day -1 prior to the second dose of bortezomib. Beginning two days after completion of melphalan infusion, patients underwent autologous hematopoietic stem cell transplant.

Melphalan, Bortezomib, Autologous Transplant

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Based on the annual number of referrals made to the Myeloma and Amyloidosis Program, expected accrual to this study was about 20 patients per year.

This study was terminated due to the investigator's departure from the institution.

Choon-kee Lee, MD

The study was terminated, study endpoints were not reached.

Maximally Tolerable Dose (MTD) of Both Melphalan and Bortezomib as Combination

Overall Study

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Participants receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16 and panobinostat PO QD on days 1, 3, 5, 8, 10, and 12 of each course. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, participants may continue carfilzomib IV on days 1, 2, 15, and 16, and panobinostat PO on days 1, 3, 5, 8, 10, and 12 of each course. If the disease becomes worse, participants can receive carfilzomib on the original dosing schedule (days 1, 2, 8, 9, 15, and 16 of each course).

Carfilzomib

Robert Orlowski

This phase I/Ib trial studies the side effects and best dose of panobinostat and carfilzomib in treating participants with multiple myeloma that has come back or that isn't responding to treatment. Carfilzomib keeps cancer cells from repairing themselves. If the cancer cells cannot repair themselves, they may die. Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving panobinostat and carfilzomib may work better in treating participants with multiple myeloma.

PRIMARY OBJECTIVES:

I. To determine the maximum recommended dose (MRD) of the combination of carfilzomib and panobinostat in patients with relapsed/refractory multiple myeloma (RRMM). (Phase I) II. To determine the overall response rate (stable disease \[SD\], minimal response \[MR\], partial response \[PR\], very good partial response \[VGPR\], near complete response/complete response \[nCR/CR\] of the combination. (Phase Ib)

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR), stable disease (SD), minimal response (MR), partial response (PR), very good partial response (VGPR), near complete response/complete response (nCR/CR). (Phase I) II. To determine the time to progression (TTP). (Phase I and Ib) III. To determine the progression free survival (PFS). (Phase I and Ib) IV. To determine the time to best response. (Phase I and Ib) V. To determine time to next therapy. (Phase I and Ib) VI. To determine duration of response. (Phase I and Ib) VII. To determine the overall response rate (SD, MR, PR, VGPR, nCR/CR) of the combination. (Phase Ib) VIII. To assess the safety of the combination. (Phase Ib)

OUTLINE: This is a phase I and Ib dose escalation study.

Participants receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16 and panobinostat orally (PO) once daily (QD) on days 1, 3, 5, 8, 10, and 12 of each course. Courses repeat every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After 8 courses, participants may continue carfilzomib IV on days 1, 2, 15, and 16, and panobinostat PO on days 1, 3, 5, 8, 10, and 12 of each course. If the disease becomes worse, participants can receive carfilzomib on the original dosing schedule (days 1, 2, 8, 9, 15, and 16 of each course).

After completion of study treatment, participants are followed up at 30 days.

Panobinostat and Carfilzomib in Treating Participants With Relapsed or Refractory Multiple Myeloma

Phase 1/1b Study of the Efficacy and Safety of the Combination of Panobinostat + Carfilzomib in Patients With Relapsed/Refractory Myeloma

Will use Kaplan-Meier methods appropriate for survival analysis.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma	NCT02353572	Plasma Cell Mye... Plasmacytosis Recurrent Plasm... Smoldering Plas...	Melphalan Bortezomib Dexamethasone Autologous Tran...	18 Years - 70 Years	University of Colorado, Denver
Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma	NCT02353572	Plasma Cell Mye... Plasmacytosis Recurrent Plasm... Smoldering Plas...	Melphalan Bortezomib Dexamethasone Autologous Tran...	18 Years - 70 Years	University of Colorado, Denver
Melphalan and Bortezomib Prior to Autologous Stem Cell Transplant in Treating Patients With Multiple Myeloma	NCT02353572	Plasma Cell Mye... Plasmacytosis Recurrent Plasm... Smoldering Plas...	Melphalan Bortezomib Dexamethasone Autologous Tran...	18 Years - 70 Years	University of Colorado, Denver
Panobinostat and Carfilzomib in Treating Participants With Relapsed or Refractory Multiple Myeloma	NCT01301807	Non-Secretory P... Plasmacytosis Recurrent Plasm... Refractory Plas...	Carfilzomib Panobinostat	18 Years -	M.D. Anderson Cancer Center

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