Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Amino Acids

Vaccines

Molgramostim

Sargramostim

Interferons

Tyrosine Kinase Inhibitors

Interferon-alpha

Imatinib Mesylate

Antiviral Agents

Immunologic Factors

Tyrosine

Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II.

Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A).

GM-K562 cell vaccine

Interferon alfa

B. Douglas Smith, MD

RATIONALE: Tyrosine kinase inhibitors may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Interferon alfa may interfere with the growth of cancer cells. GM-CSF may help cells that are involved in the body's immune response work better. Vaccines made from a person's cancer cells may help the body build an effective immune response to kill cancer cells.

PURPOSE: This randomized phase II trial is studying tyrosine kinase inhibitors, interferon alfa, and GM-CSF to see how well they work compared to tyrosine kinase inhibitors and vaccine therapy in treating patients with chronic phase chronic myelogenous leukemia.

OBJECTIVES:

Primary

* Compare clinical response, in terms of 1-year progression-free survival and rate of molecular complete remission, in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) in chronic phase who have achieved a complete cytogenetic remission to single-agent tyrosine kinase inhibitor treated with interferon alfa and sargramostim (GM-CSF) vs tyrosine kinase inhibitor and GM-K562 cell vaccine.

Secondary

* Compare time to Ph-negativity by polymerase chain reaction after randomization.
* Compare disease-free survival and percent molecular complete remissions.
* Determine the toxicity of these treatment regimens in these patients.

OUTLINE: This is a multicenter, randomized, crossover, study. Patients are randomized to 1 of 2 treatment arms. The study will be modified based on the results of the planned interim analysis. Individual Study Arms will continue to accrue and treat as indicated by the analysis. The study in its current format will continue should the planned interim analysis indicate both Study Arms remain viable as effective treatments.

All patients continue to receive their standard dose of tyrosine kinase inhibitor in addition to 1 of the following treatment arms:

* Arm I : Patients receive interferon alfa subcutaneously (SC) and GM-CSF SC once daily for 6 months. Patients who achieve a molecular complete remission (CR) (defined as BCR-ABL-negative disease confirmed by 2 PCR assays separated by 1 month) at the end of the 6-month period, discontinue study therapy and are monitored for disease recurrence by blood tests every 4 weeks. Patients who do not achieve a molecular CR (defined as BCR-ABL-positive disease) after completion of the initial 6 months of therapy, receive an additional 6 months of therapy as above. Patients who achieve BCR-ABL-negative disease during the additional 6 months of therapy, discontinue study therapy and are monitored for disease recurrence by blood tests every 4 weeks. Patients who remain BCR-ABL-positive by PCR after an additional 6 months of therapy, are eligible to cross over to arm II.

If at any time after stopping study therapy blood tests show disease recurrence, patients restart tyrosine kinase inhibitor and are eligible to cross over to arm II. Patients are also eligible to cross over to arm II in the presence of unacceptable toxicity.

* Arm II: Patients receive GM-K562 cell vaccine intradermally once every 3 weeks for a minimum of 6 months. Patients with BCR-ABL-negative disease at the end of the 6-month period discontinue study therapy and are monitored for disease recurrence by blood tests every 4 weeks. Patients with BCR-ABL-positive disease after the completion of the initial 6 months of therapy, receive an additional 6 months of therapy as above. Patients who achieve BCR-ABL-negative disease during the additional 6 months of therapy, discontinue study therapy and are monitored every 4 weeks for disease recurrence. Patients who remain BCR-ABL-positive after the additional 6 months of therapy, are eligible to cross over to arm I.

If at any time after stopping study therapy blood tests show disease recurrence, patients restart tyrosine kinase inhibitor and are eligible to cross over to arm I. Patients are also eligible to cross over to arm I in the presence of unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 1 year.

As of May 2014, Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + GM-CSF.

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

Participants were randomly assigned to Arm A or Arm B and received up to twelve months of protocol therapy. If at any point a participant progressed, relapsed, or had unacceptable toxicity, they could cross over to the other arm. Participants could only cross over once.

Interferon and GM-CSF Compared With Imatinib Mesylate and Vaccine Therapy in Patients With Chronic Phase CML on a TKI

A Randomized Phase II Trial of Interferon + GM-CSF Versus K562/GM-CSF Vaccination in CML Patients Achieving a Complete Cytogenetic Response to Frontline Tyrosine Kinase Inhibitor Therapy

Number of patients alive and without disease progression or relapse

Percentage of patients who achieved molecular remission as defined by polymerase chain reaction negativity.

Number of months from randomization to molecular remission as defined by polymerase chain reaction negativity.

Median number of days to progression of disease in participants who stopped all treatment as directed by the protocol.

Number of participants unable to complete protocol-specified treatment due to toxicity.

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adverse events were collected monthly for up to two years.

Patients will receive injections of interferon alfa and sargramostim once a day for 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm II.

Interferon alfa: Given by injection

Sargramostim: Given by injection

Arm A

Patients will receive an injection of GM-K562 cell vaccine every 3 weeks for at least 6 months. Some patients may receive treatment for up to 1 year. After 1 year, some patients may receive treatment as in arm I. NOTE: Study Arm B is not available to newly accrued and enrolled subjects based on the interim analysis directing all new subjects to the combination of Interferon + sargramostim (Arm A).

GM-K562 cell vaccine: Given by injection

Arm B

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Doug Smith, MD

Crossover participants were not analyzed for this outcome. This is as per the analysis plan written in this protocol.

Progression-free Survival

Complete Remission Rate

Time to Complete Molecular Remission

Disease-free Survival

This outcome includes all participants who were either started on an arm or crossed over to an arm.

Early Discontinuation

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Analgesics

Reproductive Control Agents

Interleukin-2

Medroxyprogesterone Acetate

Medroxyprogesterone

Interferon alpha-2

Analgesics, Non-Narcotic

Contraceptive Agents

Contraceptives, Oral

Contraceptives, Oral, Hormonal

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

Contraceptive Agents, Male

Antineoplastic Agents, Hormonal

medroxyprogesterone acetate

Sylvie Negrier, MD, PhD

The PERCY Quattro trial has been designed to evaluate the survival benefit of two cytokine treatments, Interleukin-2 (IL2) and/or alpha interferon (IFN), for patients with intermediate chance of response in metastatic renal cell carcinoma.

Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2.

The primary objective of the study is overall survival; secondary objectives are progression-free survival, response rate, toxicity, and quality of life.

The PERCY Quattro trial has been designed to evaluate the survival benefit of Interleukin-2 (IL2) and/or alpha interferon (IFN) for patients with intermediate chance of response in metastatic renal cell carcinoma.

The primary objective is overall survival, and secondary objectives are progression-free survival, response rate, toxicity, and quality of life assessed before and after induction treatment (week 10).

Patients above 18 years of age are eligible if they have histologically confirmed, clearly progressive metastatic renal carcinoma, more than one metastatic organ and good performance status (Karnofsky score ≥80%), or one metastatic organ with Karnofsky score 80%, normal blood and liver functions with creatinine level \<= 160 µmol/L.

Eligible patients will be randomly assigned in a two-by-two factorial design to either medroxyprogesterone (MPA), subcutaneous IFN, subcutaneous IL2, or a combination of IFN and IL2. The planned sample size is 456 patients (114 in each of the four arms). MPA is given orally as 200 mg daily. IFN is given subcutaneously as 9 million IU three times a week. IL2 is given subcutaneously on a four-week schedule: 9 million IU twice daily for five days followed by a two-day rest, then, on the following three weeks, 9 million IU twice daily for two days then 9 million IU once daily on the following three days; after a week of rest, an identical 4-week cycle is administered. IFN and IL2 combination is given using identical routes, schedules and doses except for a reduction of IFN dose to 6 million IU per injection.

Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis

PERCY QUATTRO: Medroxyprogesterone, Interferon Alpha-2a, Interleukin 2 or Combination of Both Cytokines in Patients With Metastatic Renal Carcinoma of Intermediate Prognosis

French Immunotherapy Intergroup

SCAPP (Sub-Cutaneous Administration Proleukin Program)

Centre Leon Berard

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Interferon alfa (Roferon) 3 MU given Sub Cutaneously three time /week for the first week, 9 MU given Sub Cutaneously three time /week for the second week, 18 MU given Sub Cutaneously three time /week thereafter.

Interferon Alfa

25 mg of CCI-779 given Intra Venously once per week

CCI-779

15 mg of CCI-779 given Intra Venously once per week; 6 MU of IFN alfa (Roferon) given Sub Cutaneously three time /week

Interferon Alfa and CCI-779

Pfizer CT.gov Call Center

The primary objective of this study is efficacy. The primary efficacy endpoint of this study is a comparison of the overall survival of subjects treated with CCI-779 \[Temsirolimus\], administered intravenously \[IV\] once weekly and the combination of CCI-779, administered IV once weekly with Interferon Alfa \[IFN alfa\] subcutaneously \[SC\] three times per week \[TIW\], compared with the overall survival of subjects treated with IFN alfa (SC TIW) alone, in poor-prognosis subjects with advanced RCC.

Study Evaluating Interferon And CCI-779 In Advanced Renal Cell Carcinoma

A Phase 3, Three-Arm, Randomized, Open-Label Study Of Interferon Alfa Alone, CCI-779 Alone, And The Combination Of Interferon Alfa And CCI-779 In First-Line Poor-Prognosis Subjects With Advanced Renal Cell Carcinoma.

Overall survival is the duration from randomization to death. For participants who are alive, overall survival is censored at the last contact.

PFS based on Independent Central Review Assessment. The period from randomization until disease progression, death or date of last contact.

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR was the disappearance of all target lesions and non target lesions. PR was at least a 30 percent (%) decrease in sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Clinical benefit: confirmed CR or PR or had stable disease (SD) lasting at least 24 weeks. CR was the disappearance of all target lesions and non target lesions. PR was at least a 30% decrease in sum of the LD of target lesions, taking as reference the baseline sum LD. SD was having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

DR: Time from first documentation of objective tumor response to first date that recurrence or progressive disease (PD) was objectively documented, taking as a reference for PD, the smallest sum LD recorded since randomization.

TTF is defined as the time from the date of randomization to the date of PD or death, withdrawal from treatment due to an adverse event (AE), withdrawal of voluntary consent, or lost to follow-up, whichever occurred first, censored at the date of the conclusion of treatment phase.

The Q-Twist is not a score calculated for each participant but is defined only on a by treatment group basis. For each treatment group, it is the weighted sum of the mean durations of the health states Tox, Twist, and Relapse. Tox is defined as time with severe toxicity related to treatment; Twist: time without symptoms or toxic side effects; and Relapse: time after relapse/progression. The mean duration of each health state is calculated based on the area under the Kaplan Meier curve pertaining to that health state. There is no direct method for calculating the "dispersion" of Q-Twist, and it is typically done using bootstrap method for purposes of inference (see, e.g., Glasziou PP, Simes RJ, Gelber RD. Quality adjusted survival analysis. Stat Med 1990; 9: 1259-76). In practice, as apparently in the case with this study, the intermediate values resulting from the bootstrap exercise were not displayed.

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. EQ-5D index measured 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Range of EQ-5D index score = -0.594 to 1 where higher scores indicated a better health state.

Pfizer

The same event may appear as both an AE and a Serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another subject, or 1 participant may have experienced both a serious and nonserious event during the study.

Interferon Alfa (Roferon) 3 million units (MU) subcutaneously 3 times per week for 1 week, then 9 MU subcutaneously 3 times per week for 1 week, then 18 MU subcutaneously 3 times per week until disease progression or treatment withdrawal

Temsirolimus (CCI-779) 25 milligrams (mg) intravenously (IV) once per week until disease progression or treatment withdrawal

Interferon Alfa (Roferon) 6 MU subcutaneously 3 times per week and Temsirolimus (CCI-779) 15 mg IV once per week until disease progression or treatment withdrawal

Interferon Alfa and Temsirolimus

Age Continuous

Efficacy data was not collected or analyzed after the primary analysis was completed.

Pfizer ClinicalTrials.gov Call Center

Intent-to-treat (ITT) Population: all randomized participants

Overall Survival (OS)

Progression-Free Survival (PFS)

Percentage of Participants With Objective Response

Percentage of Participants With Clinical Benefit

ITT subset of participants who had a response

Duration of Response (DR)

Time to Treatment Failure (TTF)

Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST)

ITT;(N)=participants with evaluable data. Week 12 and 32 data collected for individual participants but not summarized.

European Quality of Life Health Questionnaire (EQ-5D) - Index Score

Skin and Connective Tissue Diseases

Recurrence

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Aldesleukin

Cisplatin

Lenograstim

Vinblastine

Dacarbazine

Anti-HIV Agents

Anti-Retroviral Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Tubulin Modulators

Antimitotic Agents

Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.

Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

interleukin-2

filgrastim

interferon alfa

cisplatin

dacarbazine

vinblastine

Lawrence E. Flaherty, MD

John A. Thompson, MD

John T. Vetto, MD, FACS

Michael B. Atkins, MD

John M. Kirkwood, MD

Frank Haluska, MD, PhD

Alberto S. Pappo, MD

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2, in treating patients who have melanoma.

OBJECTIVES:

* Compare the overall survival and disease-free survival of patients with high-risk melanoma treated with interferon alfa vs cisplatin, vinblastine, and dacarbazine plus interferon alfa and interleukin-2.
* Compare the toxic effects of these treatment regimens in these patients.
* Determine the relationship between minimal residual disease (MRD) status at 12 weeks and 52 weeks and overall survival of patients treated with these regimens.
* Compare the effects of these treatment regimens on the MRD status of these patients.
* Determine the relationship between clinical characteristics (number of involved lymph nodes, ulcerated primary, and extracapsular extension) and MRD in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (N1 or N2 vs N3), degree of lymph node involvement (micrometastases only vs any macrometastases, including satellite/in-transit metastases), and ulceration of the primary tumor (yes vs no vs unknown primary). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 410 patients (205 per treatment arm) will be accrued for this study within 3 years.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Interferon and GM-CSF Compared With Imatinib Mesylate and Vaccine Therapy in Patients With Chronic Phase CML on a TKI	NCT00363649	Leukemia	GM-K562 cell va... Interferon alfa Sargramostim	18 Years - 120 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis	NCT00291369	Metastatic Rena...	Interleukin-2 Interferon alfa medroxyprogeste...	18 Years -	Centre Leon Berard
Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis	NCT00291369	Metastatic Rena...	Interleukin-2 Interferon alfa medroxyprogeste...	18 Years -	Centre Leon Berard
Interferon and GM-CSF Compared With Imatinib Mesylate and Vaccine Therapy in Patients With Chronic Phase CML on a TKI	NCT00363649	Leukemia	GM-K562 cell va... Interferon alfa Sargramostim	18 Years - 120 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Evaluating Interferon And CCI-779 In Advanced Renal Cell Carcinoma	NCT00065468	Carcinoma, Rena... Kidney Neoplasm...	Interferon Alfa CCI-779 Interferon Alfa...	18 Years -	Pfizer
S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma	NCT00006237	Melanoma (Skin)	interleukin-2 filgrastim interferon alfa cisplatin dacarbazine vinblastine	18 Years -	SWOG Cancer Research Network
COVID-19 Prevention and Treatment in Cancer; a Sequential Multiple Assignment Randomised Trial;	NCT04534725	Cancer Covid19 Respiratory Vir...	Interferon alfa Selinexor Lenzilumab	18 Years -	Peter MacCallum Cancer Centre, Australia
S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma	NCT00006237	Melanoma (Skin)	interleukin-2 filgrastim interferon alfa cisplatin dacarbazine vinblastine	18 Years -	SWOG Cancer Research Network
Determining the Maximum Tolerated Dose of Low Dose Interferon-alpha in Conjunction With Nilotinib in Pretreated Philadelphia Chromosome Positive (Ph+) Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP)	NCT01220648	Chronic Myeloid...	Nilotinib, inte...	18 Years -	Novartis
Post-Operative Adjuvant Radiotherapy With Concurrent Interferon-Alfa	NCT00005615	Melanoma (Skin)	Interferon alfa Radiation thera...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for interferon alfa