Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Anti-Infective Agents

Dexamethasone

Androgens

Dexamethasone acetate

Acyclovir

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antiviral Agents

Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient.

Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle.

Carfilzomib

Administered prior to administration of Study drug

Guru Sonpavde, MD

Mansoor Saleh, MD

This study will test how effective the drug, Carfilzomib, reduces progression of prostate cancer in patients who have previously received chemotherapy and androgen inhibitors. Carfilzomib is approved for multiple myeloma but is not approved for prostate cancer. Therefore, it is considered investigational. Other approved methods of treatment for metastatic prostate cancer have demonstrated only modest benefits. Novel and tolerable agents are necessary to make further gains and extend overall survival.

First-line chemotherapy for metastatic castration-resistant prostate cancer (CRPC) combined with androgen inhibitors modestly extends overall survival. Carfilzomib is anticipated to enhance progression-free survival (PFS) as well as reduce pain and toxicities.

Proteasome inhibitors are promising agents used in the therapy of prostate cancer. Carfilzomib is a more potent and irreversible proteasome inhibitor than the frequently used proteasome inhibitor, Bortezomib. In Phase I trials Carfilzomib demonstrated substantial antitumor activity while exhibiting tolerable side effects.

Carfilzomib has been approved by the FDA for patients with multiple myeloma. The drug, however, is not approved for the use with CRPC patients. This trial will evaluate the tolerance and effectiveness of Carfilzomib in men with metastatic progressive CRPC following chemotherapy and androgen inhibitors.

Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment

A Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Chemotherapy and Androgen Pathway Inhibitors

The study will measure patient survival at 6 months but will continue to monitor overall survival as a secondary objective. The Kaplan-Meier method will be used.

Outcome measure was completed by using a count of participants.

PSA levels were collected at each visit on the day of treatment. Linear regression with PSA as the dependent variable and time as the dependent variable was performed.

The CTC marker will be used to evaluate efficacy of response to treatment. CTC changes will include changes from unfavorable (less than or equal to 5/7.5 ml) to favorable and declines by \>30%.

Three collections: before study initiation, Day 1 of Cycles 2 and 4

Hematologic and non-hematologic toxicities will be graded. The new international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) will serve as the guideline.

On Day 1 of each cycle (4 weeks) for the duration of treatment and then 30 days following the last treatment

Amgen

University of Alabama at Birmingham

Principal Investigator

Carfilzomib is administered twice-weekly on consecutive days (days 1, 2, 8, 9, 15, 16) as a 30-minute intravenous infusion for 3 weeks every 4 weeks (1 cycle) with dexamethasone given as pre-medication. The dose of carfilzomib is 20 mg/m2 on days 1 and 2 of cycle 1 and is then escalated in succeeding weeks and cycles to 56 mg/m2 if no dose limiting toxicities occur. Acyclovir is given orally at 400 mg twice daily during therapy but may be discontinued at some point. Therapy will continue until side effects become unacceptable, the disease progresses, or the doctor withdraws the patient.

Carfilzomib: Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 within each 4 week cycle.

Dexamethasone: Administered prior to administration of Study drug

Acyclovir: Administered orally twice daily

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Pam Dixon, RN, BSN, OCN

8 patients did not complete treatment and were not included in the analysis.

Progression-free Survival (PFS)

8 patients did not complete treatment and were lost to follow up

Overall Survival

We were unable to collect blood specimen for PSA analysis for 1 patient.

Number of Participants With Prostate-Specific Antigen (PSA) Changes

1 patient did not have blood draw. 27 patients had blood draws for CTC enumeration across baseline, Cycle 2 day 1 and cycle 4 day 1.

Number of Participants With Circulating Tumor Cell (CTC) Decline Over Three Time Points (Before Study Initiation, Day 1 of Cycles 2 and 4

Anemia (>= Grade 3 or 4)

Hypertension (>= Grade 3 or 4)

All serious adverse events and \> grade 3 toxicities were reported for patients who received treatment with Carfilzomib

Assessment of Toxicities

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Philadelphia Chromosome

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Translocation, Genetic

Chromosome Aberrations

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Lymphosarcoma

Micronutrients

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Pharmaceutical Solutions

Bone Density Conservation Agents

Anti-Dyskinesia Agents

Hematinics

Vitamins

Amino Acids

Leucovorin

Cytarabine

Cyclophosphamide

Levoleucovorin

Methotrexate

Vincristine

Ophthalmic Solutions

Daunorubicin

Calcium

Lenograstim

Mercaptopurine

Calcium, Dietary

Asparaginase

Alemtuzumab

Trimethoprim, Sulfamethoxazole Drug Combination

Trimethoprim

Sulfamethoxazole

Allopurinol

Imatinib Mesylate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antidotes

Protective Agents

Trace Elements

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antineoplastic Agents, Immunological

Antioxidants

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Cytochrome P-450 Enzyme Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

allopurinol

cyclophosphamide

daunorubicin hydrochloride

vincristine sulfate

dexamethasone

asparaginase

filgrastim

imatinib mesylate

methotrexate

cytarabine

trimethoprim-sulfamethoxazole

mercaptopurine

leucovorin calcium

alemtuzumab

acyclovir

laboratory biomarker analysis

pharmacological study

Wendy Stock

This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy also work in different ways to kill cancer cells or stop them from growing. Giving alemtuzumab together with combination chemotherapy may be a better way to block cancer growth.

PRIMARY OBJECTIVES:

I. To determine the feasibility and toxicity profiles of escalating doses of Campath-1H (alemtuzumab) given subcutaneously during post-remission intensification treatment of adults with acute lymphoblastic leukemia (ALL).

II. To determine the disease-free survival (DFS) and overall survival (OS) when Campath-1H is used during post-remission intensification treatment of adults with ALL.

III. To determine whether antibody treatment with Campath-1H can further reduce minimal residual disease states in adult ALL.

IV. To obtain preliminary descriptive data on serum levels of Campath-1H during course IV, module D using limited pharmacokinetic sampling during the phase I and II components of the study.

V. To obtain feasibility data on the addition of imatinib to Cancer and Leukemia Group B (CALGB) induction and postremission combination chemotherapy for patients with Philadelphia chromosome positive (Ph+) ALL.

OUTLINE: This is a dose-escalation study of alemtuzumab.

COURSE 1 (module A): Patients receive allopurinol orally (PO) 4 times daily (QID) on days 1-14, cyclophosphamide\* intravenously (IV) over 15-30 minutes on day 1, daunorubicin hydrochloride IV on days 1-3, vincristine sulfate IV on days 1, 8, 15, and 22, dexamethasone PO twice daily (BID) on days 1-7 and 15-21, asparaginase subcutaneously (SC) on days 5, 8, 11, 15, 18, and 22, and filgrastim SC on days 4-11. Patients who are Ph+ also receive imatinib mesylate PO on days 15-28.

\*Note: Patients who are = 60 years old do not receive cyclophosphamide.

COURSE 2 (module B): Patients receive methotrexate intrathecally (IT) on day 1, cytarabine IV over 3 hours on days 1-3, dexamethasone as eye drops QID on days 1-4, trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-29, and cyclophosphamide, asparaginase and filgrastim as in course 1. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28.

COURSE 3 (module C): Patients receive vincristine sulfate IV on days 1, 15, and 29, methotrexate IV over 3 hours and IT on days 1, 15, and 19, methotrexate PO every 6 hours on days 1-2, 15-16, and 29-30, mercaptopurine PO on days 1-35, leucovorin calcium IV on days 2, 16, and 30, leucovorin calcium PO every 6 hours on days 3-4, and trimethoprim-sulfamethoxazole PO BID 3 times weekly on days 1-43. Patients who are Ph+ also receive imatinib mesylate PO on days 1-42.

COURSE 4 (module D): Patients receive alemtuzumab SC 3 times weekly for 4 weeks and begin acyclovir PO QID for 6 months (continuing through course 8).

* Phase I Cohort 1: 10 mg
* Phase I Cohort 2: 20 mg
* Phase I Cohort 3/Phase II MTD: 30 mg

COURSE 5 (module A): Patients repeat course 1, minus allopurinol.

COURSE 6 (module B): Patients repeat course 2.

COURSE 7 (module C): Patients repeat course 3.

COURSE 8: Patients receive mercaptopurine PO, vincristine sulfate IV on day 1, dexamethasone PO on days 1-5, methotrexate PO on days 1, 8, 15, and 22, and trimethoprim-sulfamethoxazole PO BID 3 days weekly. Patients who are Ph+ also receive imatinib mesylate PO on days 1-28. Courses repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 10 years.

Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)

The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data.

The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV.

Minimal Residual Disease measures the presence of of circulating leukemia cells in the body. Patients that report a Complete Response (CR) during treatment are further tested to determine the presence of small amounts of circulating leukemia cells. Here we report the number of patients who were MRD negative.

Disease Free Survival (DFS) is defined as the time from a Complete Response (CR) until death or relapse. The date of last clinical assesment will be used as the censor date for patients with no death or relapse. The DFS will be estimated using the Kaplan-Meier method with confidence intervals presented.

Overall Survival is defines as the time from registration to death due to any cause. It is estimated using the Kaplan-Meier method with confidence intervals presented.

National Cancer Institute (NCI)

See detailed description or participant flow.

Phase I - Alemtuzumab and Combination Chemotherapy

Phase II - Alemtuzumab and Combination Chemotherapy

Total

Age, Continuous

Wendy Stock, M.D.

Only participants who started Alemtuzumab were analyzed per study design. Specifically, one patient declined Alemtuzumab and was excluded from this analysis.

Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I)

Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II)

Patients who reported a Complete Response (CR) during treatment and were analyzed for the presence of circulating leukemia cells.

Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II)

All patients who received protocol treatment and had a complete response (CR) during treatment were included in this analysis. Phase I patients, who achieved complete response, were included with the phase II patients, who achieved complete response, for this analysis.

Disease-free Survival, for Only Complete Response Patients

All patients who registered, received protocol treatment, and were eligible were evaluated for this endpoint. Phase I patients were included with the phase II patients for this analysis.

A complete remission (CR) requires the following: an absolute neutrophil count (segs and bands) \> 1500/μl, no circulating blasts, platelets \> 100,000/μl; bone marrow cellularity \> 20% with trilineage hematopoiesis, and \< 5% marrow blast cells, none of which appear neoplastic. All previous extramedullary manifestations of disease must be absent (e.g., lymphadenopathy, splenomegaly, skin or gum infiltration, testicular masses, or CNS involvement).

Three participants were deemed ineligible and excluded from this analysis.

Number of Participants Achieving Complete Remission

COURSE 1-allopurinol (ALL) orally (PO) 4x daily (QID) d1-14, cyclophosphamide (CTX) intravenously (IV) d1, daunorubicin IV d1-3, vincristine (VCR) IV d1,8,15 \& 22, dexamethasone (DEX) PO 2x daily (BID) d1-7 \& 15-21, asparaginase (APG) subcutaneously (SC) d5,8,11,15,18 \& 22, and filgrastim (FIL) SC d4-11. Ph+ pts imatinib (IMT) PO d15-28 COURSE 2-methotrexate (MTX) intrathecally (IT) d1, cytarabine IV d1-3, DEX eye drops QID d1-4, cotrimoxazole (CRT) PO BID 3x wkly d1-29 and CTX, APG \& FIL as course 1. Ph+ pts IMT PO d1-28 COURSE 3-VCR IV d1,15 \& 29, MTX IV \& IT d1,15 \& 19, MTX PO q6 hr d1-2,15-16 \& 29-30, mercaptopurine (6-MP) PO d1-35, leucovorin (LCV) IV d 2,16 \& 30, LCV PO q6 hr d3-4 \& CRT PO BID 3x wkly d1-43. Ph+ pts IMT PO d1-42 COURSE 4-alemtuzumab 10,20 or 30 mg SC 3x wkly q4 wk, acyclovir PO QID q6 mo COURSE 5-course 1 COURSE 6-course 2 COURSE 7-course 3 COURSE 8-6-MP PO, VCR IV d1, DEX PO d1-5, MTX PO d1,8,15 \& 22 and CRT PO BID 3d wkly. Ph+ pts IMT PO d1-28 q24 mo

COURSE 1-allopurinol (ALL) orally (PO) 4x daily (QID) d1-14, cyclophosphamide (CTX) intravenously (IV) d1, daunorubicin IV d1-3, vincristine (VCR) IV d 1,8,15 \& 22, dexamethasone (DEX) PO 2x daily (BID) d 1-7 \& 15-21, asparaginase (APG) subcutaneously (SC) d 5,8,11,15,18 \& 22, and filgrastim (FIL) SC d 4-11. Ph+ pts imatinib (IMT) PO d 15-28 COURSE 2-methotrexate (MTX) intrathecally (IT) d1, cytarabine IV d1-3, DEX eye drops QID d 1-4, cotrimoxazole (CRT) PO BID 3x wkly d1-29 and CTX, APG \& FIL as course 1. Ph+ pts IMT PO d1-28 COURSE 3-VCR IV d 1,15 \& 29, MTX IV \& IT d 1,15 \& 19, MTX PO q6 hr d 1-2,15-16 \& 29-30, mercaptopurine (6-MP) PO d1-35, leucovorin (LCV) IV d 2,16 \& 30, LCV PO q6 hr d 3-4 \& CRT PO BID 3x wkly d1-43. Ph+ pts IMT PO d1-42 COURSE 4-alemtuzumab 30 mg SC 3x wkly q4 wk, acyclovir PO QID q6 mo COURSE 5-course 1 COURSE 6-course 2 COURSE 7-course 3 COURSE 8-6-MP PO, VCR IV d1, DEX PO d1-5, MTX PO d 1,8,15 \& 22 and CRT PO BID 3x wkly. Ph+ pts IMT PO d1-28 q24 mo

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment	NCT02047253	Metastatic Cast...	Carfilzomib Dexamethasone Acyclovir	19 Years -	University of Alabama at Birmingham
Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia	NCT00061945	Acute Undiffere... B-cell Adult Ac... B-cell Childhoo... L1 Adult Acute ... L1 Childhood Ac... L2 Adult Acute ... L2 Childhood Ac... Philadelphia Ch... Philadelphia Ch... Philadelphia Ch... T-cell Adult Ac... T-cell Childhoo... Untreated Adult... Untreated Child...	allopurinol cyclophosphamid... daunorubicin hy... vincristine sul... dexamethasone asparaginase filgrastim imatinib mesyla... methotrexate cytarabine trimethoprim-su... mercaptopurine leucovorin calc... alemtuzumab acyclovir laboratory biom... pharmacological...	15 Years -	National Cancer Institute (NCI)
Treatment and Suppression of Hairy Leukoplakia in ARC Patients With Oral Acyclovir (ACV)	NCT00002026	Leukoplakia, Ha... HIV Infections	Acyclovir	18 Years -	NIH AIDS Clinical Trials Information Service
Effect of Body Mass on Acyclovir Pharmacokinetics	NCT01714180	Hematological M... Pharmacokinetic...		18 Years -	West Virginia University
Intralesional Vitamin D3 Versus Intralesional Acyclovir in Treatment of Plantar Warts	NCT05324904	Plantar Wart	Vitamin D acyclovir	12 Years - 70 Years	Assiut University
Intralesional Vitamin D3 Versus Intralesional Acyclovir in Treatment of Plantar Warts	NCT05324904	Plantar Wart	Vitamin D acyclovir	12 Years - 70 Years	Assiut University
Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma	NCT02073097	Contiguous Stag... Noncontiguous S... Stage I Adult D... Stage III Adult... Stage IV Adult ...	Carfilzomib Rituximab Cyclophosphamid... Doxorubicin hyd... Vincristine sul... Prednisone Pegfilgrastim Acyclovir	18 Years -	Case Comprehensive Cancer Center
Effect of Body Mass on Acyclovir Pharmacokinetics	NCT01714180	Hematological M... Pharmacokinetic...		18 Years -	West Virginia University

Spots Global Cancer Trial Database for acyclovir

Every month we try and update this database with for acyclovir cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for acyclovir

Every month we try and update this database with for acyclovir cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for acyclovir cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.