Neoplasms

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Melphalan

Lenograstim

Proteasome Inhibitors

Immunologic Factors

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Alkylating Agents

Immunosuppressive Agents

Phase I/II study on the backbone of high-dose melphalan on day -2 pre-autologous hematopoietic cell transplantation (AHCT)

•Addition of an increasing number of doses of Carfilzomib (CFZ) in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects:

Cohort 1: add CFZ 20 mg/m\^2 intravenous (IV) on days +1, +2

Cohort 2 : add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9

Cohort 3: add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following engraftment: CFZ 20 mg/m\^2 IV given on days 42-43 then CFZ 56 mg/m\^2 IV given on days 49-50, 56-57, then on days 70.

Carfilzomib

Filgrastim

Ronald E Gress, M.D.

Background:

- Plasma cell myeloma is a type of cancer that affects the plasma cells in the bone marrow. It can be difficult to treat with chemotherapy. One possible treatment combines chemotherapy with a stem cell transplant. To make this treatment more effective, researchers want to give another drug along with the transplant. This drug, carfilzomib, is often used to help treat plasma cell myeloma. However, it is not usually given along with the transplant. Researchers want to see if it is safe and effective to combine the stem cell transplant with carfilzomib, and if it improves the results of the transplant.

Objectives:

- To test the safety and effectiveness of carfilzomib given with stem cell transplant for plasma cell myeloma.

Eligibility:

- Individuals between 18 and 75 years of age who are having a stem cell transplant to treat plasma cell myeloma.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and a bone marrow biopsy will also be performed.
* Participants will have their own stem cells collected for the transplant. The transplant will be performed according to the standard of care.
* All participants will receive carfilzomib on the first 2 days after transplant. The study doctors will determine the number of additional doses that they may have.
* Treatment will be monitored with frequent blood tests and imaging studies.

Background:

* Despite very significant progress in therapy for plasma cell myeloma (PCM) in the last decade, the disease remains mostly incurable.
* High-dose chemotherapy followed by autologous hematopoietic cell transplantation (AHCT) continues to be a critical component of early treatment for PCM, but it is clear that the disease is not eradicated by the present high-dose therapy strategy, while intensifying the preparative regimen has, to this day, resulted in either no improvement in disease control or increased toxicity.
* Carfilzomib (CFZ) is a newer proteasome inhibitor with increased activity and a safer toxicity profile than bortezomib in PCM. The favorable toxicity profile makes it a likely candidate for increasing anti-PCM drug exposure in the early post-AHCT period.

Objectives:

Primary Objectives

-Evaluate feasibility and toxicity of an increasing number of doses of CFZ administered in the early period post-AHCT for PCM

Secondary Objective

* Evaluate the immune reconstitution post-AHCT following CFZ therapy
* Evaluate the effects of the addition of CFZ in the early post-AHCT period on the response rate at day 100 post-AHCT

Eligibility:

* Newly diagnosed subjects with PCM following induction therapy
* Subjects with documentation of persistent/refractory disease who have received no more than 2 salvage regimens following relapse and who have not undergone AHCT
* Adequate organ functions with no major co-morbidity
* Age greater than 18 years and less than or equal to 75 years

Design:

* Phase I/II study on the backbone of high-dose melphalan on day -2 pre-AHCT
* Addition of an increasing number of doses of CFZ in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects:

Cohort 1: add CFZ 20 mg/m\^2 on days +1, +2

Cohort 2 : add CFZ 20 mg/m\^2 on days: +1, +2, +8, +9

Cohort 3: add CFZ 20 mg/m\^2 on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following

engraftment: CFZ 20 mg/m\^2 given on days 42-43 then CFZ 56 mg/m\^2 given on days 49-50, 56-57, then on days 70-71, 77-78 and 84-85

-Dose-limiting toxicity, incidence of engraftment failure and treatment-related mortality are the objects of early stopping rules for safety purposes

Carfilzomib and Stem Cell Transplant for Plasma Cell Myeloma

Phase I / II Study Of Carfilzomib (CFZ) Intensification Early After Autologous Transplantation (AHCT) For Plasma Cell Myeloma

Engraftment failure is defined as the failure to achieve neutrophil engraftment by day 21; defined from day 0, day of autologous hematopoietic cell transplantation (AHCT), as the first of three consecutive days on which the patient's absolute neutrophil count is greater than 0.5x10(9)/l following the nadir. Transplant related mortality is defined as any subject who dies in the first 100 days post-AHCT of any non-relapse related cause.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

National Cancer Institute (NCI)

Principal Investigator

Cohort 1- CFZ 20 mg/m^2 (Day 1,2)

Cohort 2- CFZ 20 mg/m^2 (Day 1,2,8,9)

Cohort 3-CFZ 20 mg/m^2 (Day1,2,8,9/AHCT)

Total

<=18 years

Between 18 and 65 years

>=65 years

Age, Categorical

Age, Continuous

Female

Male

Gender

Hispanic or Latino

Not Hispanic or Latino

Unknown or Not Reported

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Native Hawaiian or Other Pacific Islander

Black or African American

White

More than one race

Race (NIH/OMB)

United States

Region of Enrollment

The study was closed prematurely because the investigator left the National Institutes of Health.

Dr. Ronald Gress

Engraftment Failure Transplant Related Mortality

Analysis of dose limiting toxicities (DLTs) was planned but not performed due to study termination; this Outcome Measure captures any events that occurred.

Number of Participants With Adverse Events

Phase I/II study on the backbone of high-dose melphalan on day -2 pre-autologous hematopoietic cell transplantation (AHCT)

•Addition of an increasing number of doses of Carfilzomib (CFZ) in the early post-AHCT period introduced in a step-wise fashion in 3 successive cohorts of 3 to 15 subjects:

Cohort 1: add CFZ 20 mg/m\^2 intravenous (IV) on days +1, +2

Cohort 2 : add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9

Cohort 3: add CFZ 20 mg/m\^2 IV on days: +1, +2, +8, +9 and add an early post-AHCT consolidation following engraftment: CFZ 20 mg/m\^2 IV given on days 42-43 then CFZ 56 mg/m\^2 IV given on days 49-50, 56-57, then on days 70.

Carfilzomib

Melphalan

Filgrastim

This outcome measure was not done because the study was closed prematurely because the investigator left the National Institutes of Health.

Evaluate the Immune Reconstitution Post-Pre-autologous Hematopoietic Cell Transplantation (AHCT) Following Carfilzomib (CFZ) Therapy

Evaluate the Effects of the Addition of Carfilzomib (CFZ) in the Early Post-Pre-autologous Hematopoietic Cell Transplantation (AHCT) Period on the Response Rate at Day 100 Post-AHCT

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Carfilzomib and Stem Cell Transplant for Plasma Cell Myeloma	NCT01658904	Multiple Myelom... Leukemia, Plasm...	Carfilzomib Melphalan Filgrastim	18 Years - 75 Years	National Institutes of Health Clinical Center (CC)
Carfilzomib and Stem Cell Transplant for Plasma Cell Myeloma	NCT01658904	Multiple Myelom... Leukemia, Plasm...	Carfilzomib Melphalan Filgrastim	18 Years - 75 Years	National Institutes of Health Clinical Center (CC)

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