NCT01057225 · REGISTRY CONDITION SEARCH

Cyclophosphamide, Carfilzomib, Thalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Active Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2017-12-12

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the tumor. Giving combination chemotherapy together with carfilzomib and thalidomide may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of carfilzomib when given together with cyclophosphamide, thalidomide, and dexamethasone in treating patients with newly diagnosed active multiple myeloma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Maximum Tolerated Dose (Phase I)

→

outcome · POSTED

Percentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II)

→

outcome · POSTED

Progression-free Survival (Phase II)

→

outcome · POSTED

Time to Treatment Failure

→

outcome · POSTED

Stem Cell Collection and Engraftment (Phase II)

→

outcome · POSTED

Complete Response (Phase II)

→

outcome · POSTED

Survival Time (Phase II)

→

outcome · POSTED

Progression Free Survival (12 Month)

→

outcome · POSTED

Progession Free Survival (24 Month)

→

outcome · POSTED

Overall Survival (12 Month)

→

outcome · POSTED

Overall Survival (24 Month)

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion * Creatinine =\< 2 mg/dL * Calculated Creatinine Clearance \>= 30 mL/min * Total Bilirubin =\< 2.0 mg/dL * Alkaline Phosphatase =\< 3 x ULN * ALT =\< 3 x ULN * Absolute neutrophil count \>= 1000/uL * Platelet \>= 75000/uL * Hemoglobin \>= 8.0 g/dL * Untreated symptomatic myeloma: Prior non-systemic therapy for the treatment of solitary plasmacytoma is permitted, but \>= 1 month should have elapsed from the last day of radiation; prior therapy with clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the Principal Investigator * Prior high dose corticosteroid therapy for twelve days (480 mg total dose) or less is permitted for emergent complications from newly diagnosed multiple myeloma * Measurable disease of multiple myeloma, as defined by at least ONE of the following: * Serum monoclonal protein \>= 1.0 g by protein electrophoresis * OR \> 200 mg of monoclonal protein in the urine on 24 hour electrophoresis * OR serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; OR monoclonal bone marrow plasmacytosis \>= 30% (evaluable disease) * ECOG performance status (PS) 0, 1, 2; ECOG PS of 3 will be allowed if secondary to pain in the opinion of the Investigator * Willingness and able to provide informed written consent * Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only * Willingness to return to Mayo Clinic enrolling institution for follow-up Exclusion * MGUS or smoldering myeloma * Peripheral sensory neuropathy \>= Grade 2 as defined by CTEP Active Version of the CTCAE * Active malignancy with the exception of non melanoma skin cancer or in situ cervical or breast cancer * Pregnant women or women of reproductive ability who are unwilling to use effective contraception * Nursing women * Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment * Known hypersensitivity, allergy or inability to tolerate any of the agents employed * Active, uncontrolled infection * Severe cardiac comorbidity * New York Heart Association Class III or IV Heart Failure * Recent history of myocardial infarction in the six months prior to registration * Uncontrolled angina or electrocardiographic evidence of acute ischemia * Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities * Cardiac amyloidosis with hypotension (systolic BP less than 100 mmHg) * 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 * The following medications are not permitted during the trial: any other investigational treatment; any cytotoxic chemotherapy; any other systemic anti-neoplastic therapy including, but not limited to, immunotherapy, hormonal therapy, or monoclonal antibody therapy * Palliative radiation therapy is permitted if clinically indicated and not indicative of progressive disease
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28.
intervention Names
Drug: carfilzomib
Drug: cyclophosphamide
Drug: thalidomide
Drug: dexamethasone
label
Arm I
type
EXPERIMENTAL

interventions

arm Group Labels
Arm I
description
Given IV
name
carfilzomib
other Names
PR-171
type
DRUG
arm Group Labels
Arm I
description
Given orally
name
cyclophosphamide
other Names
CPM
CTX
Cytoxan
Endoxan
Endoxana
Enduxan
type
DRUG
arm Group Labels
Arm I
description
Given orally
name
thalidomide
other Names
alpha-phthalimidoglutarimide
Contergan
Kevadon
Synovir
THAL
Thalomid
type
DRUG
arm Group Labels
Arm I
description
Given orally
name
dexamethasone
other Names
Aeroseb-Dex
Decaderm
Decadron
Decaspray
DM
DXM
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 64
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, possibly) in the first or second cycle for patients enrolled to Dose Levels -1 and 0 and in the first cycle only for patients enrolled to Dose Levels 1 and 2. We are reporting the number of DLTs
measure
Maximum Tolerated Dose (Phase I)
time Frame
From baseline to end of active treatment, up to 12 28-day cycles.
description
The proportion of patients who have at least a confirmed very good partial response will be calculated by taking the number of patients with a very good partial response or a complete response divided by the total number of patients. A complete response is defined as: * Negative immunofixation of the serum and urine * If at on study, only the measurable non-bone marrow parameter was FLC, normalization of FLC ratio * \< 5% plasma cells in bone marrow * Disappearance of any soft tissue plasmacytomas A very good partial response is defined as: * Serum and urine M-component detectable by immunofixation but not on electrophoresis or * If at on study, serum measurable, ≥ 90% or greater reduction in serum Mcomponent * Urine M-component \<100 mg per 24 hour
measure
Percentage of Patients Who Have at Least a Confirmed Very Good Partial Response (Phase II)
time Frame
Following the first 4 cycles of treatment (28 day cycles)

secondary Outcomes

description
PFS was defined as the time from registration to progression or death due to any cause. Progression was defined as any one or more of the following: • Increase of 25% from lowest confirmed response in: Serum M-component (absolute increase must be ≥ 0.5 g/dl)c Urine M-component (absolute increase must be ≥ 200 mg/24 hour) If at on study, only the measurable non-bone marrow parameter was FLC, the difference between involved and uninvolved FLC levels (absolute increase must be \>10 mg/dl) Bone marrow plasma cell percentage (absolute % must be 10%)d Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas • Development of hypercalcemia (corrected serum calcium \>11.5 mg/dl) that can be attributed solely to the plasma cell proliferative disorder
measure
Progression-free Survival (Phase II)
time Frame
From baseline to progression or death up to 3 years
description
The time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they were removed from treatment. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier
measure
Time to Treatment Failure
time Frame
From baseline to end of active treatment
description
For patients going on to stem cell collection, the total number of CD34 positive cells collected per collection, days to platelets over 20,000 without transfusion and ANC over 1000 will be recorded. If a patient fails to collect adequate stem cells for transplant, this will be recorded as such. The number of patients with successful stem cell mobilization are reported.
measure
Stem Cell Collection and Engraftment (Phase II)
time Frame
Following the first 4 courses of treatment
description
In patients continuing beyond 4 cycles the ability to induce complete response will be evaluated at completion of planned therapy.
measure
Complete Response (Phase II)
time Frame
Following the first 4 courses of treatment
description
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier
measure
Survival Time (Phase II)
time Frame
From baseline to death
description
Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression 1 day post-registration. This is reported as the percentage of patients alive and progression free at the 12 month mark.
measure
Progression Free Survival (12 Month)
time Frame
12 months
description
Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression 1 day post-registration. This is reported as the percentage of patients alive and progression free at the 24 month mark.
measure
Progession Free Survival (24 Month)
time Frame
24 months
description
12 Month Overall survival is defined as the proportion of patients to still be alive after 12 months.
measure
Overall Survival (12 Month)
time Frame
From baseline to death
description
24 Month Overall survival is defined as the proportion of patients to still be alive after 24 months.
measure
Overall Survival (24 Month)
time Frame
From baseline to death

Full study description

brief Summary: RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Thalidomide may stop the growth of cancer cells by blocking blood flow to the tumor. Giving combination chemotherapy together with carfilzomib and thalidomide may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of carfilzomib when given together with cyclophosphamide, thalidomide, and dexamethasone in treating patients with newly diagnosed active multiple myeloma.
detailed Description: PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose of carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone. (Phase I) II. In newly diagnosed myeloma to evaluate the response rate (CR, nCR, and VGPR) to carfilzomib given in combination with oral cyclophosphamide and thalidomide and dexamethasone after four 28 day cycles. (Phase II) SECONDARY OBJECTIVES: I. Determine the overall response rate (CR, nCR, PR) after 4, 8, 12 cycles. II. Determine the duration of progression-free and overall survival for patients receiving this regimen. III. To evaluate the incidence of toxicities for this regimen. IV. To evaluate the ability to successfully collect peripheral blood stem cells following four months of combination therapy. OUTLINE: This is a phase I, dose escalation study of carfilzomib followed by a phase II study. Patients receive carfilzomib IV on days 1, 2, 8, 9, 15, and 16; oral cyclophosphamide on days 1, 8, and 15; oral dexamethasone on days 1, 8, 15, and 22; and oral thalidomide on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3 months, then every 3 months for 1 year, and then every 6 months for up to 3 years.

Source references

Source notices and limitations

Discovery and provenance

release id
ctgov-registry-1336d216cbd1bbff780dac70
edge id
nct-edge-5184112efe797b1c0066
requested nct id
NCT01057225
primary nct id
NCT01057225
source kind
ctgov_condition_query
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true
source record id
Source null
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
payload sha256
b9bcbf29207e37ce07394379206fecd15bba381de6a905dad996af051181d9f4
payload
clinical indication matching status
condition_index_match_asserted_by_registry_not_reviewed
end exclusive
true
id
nct-edge-5184112efe797b1c0066
link basis
returned_by_explicit_condition_and_posted_results_filter_query
nct id
NCT01057225
occurrences
context exact
NCT01057225
end
11
exact text
NCT01057225
start
0
offset unit
unicode_code_points
query cond
Plasma Cell Neoplasms
query disease state id
ds-plasma-cell-neoplasms
source file
/Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
source file sha256
2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
source json pointer
/studies/162/protocolSection/identificationModule/nctId
source kind
ctgov_condition_query
source record id
Source null
source string basis
parsed_JSON_string_unmodified
source string sha256
5b8a4dfd8a6fc99c16deaa35a591187377766ad5ffca33ff9ec31c097176017a
source url
https://clinicaltrials.gov/api/v2/studies?query.cond=Plasma+Cell+Neoplasms&filter.advanced=AREA%5BHasResults%5Dtrue&pageSize=1000&format=json&countTotal=true

Preserved source evidence · Not medical advice