Aprepitant, Granisetron, & Dexamethasone in Preventing Nausea & Vomiting in Pts. Receiving Cyclophosphamide Before a Stem Cell Transplant

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00293384
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 40
• Location: 1
• Arm: 1
• Duration (Months): 88
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Antiemetic drugs, such as aprepitant, granisetron, and dexamethasone, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy.

PURPOSE: This clinical trial is studying how well giving aprepitant together with granisetron and dexamethasone works in preventing nausea and vomiting in patients receiving cyclophosphamide before undergoing an autologous stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nausea and Vomiting; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor	Drug: Aprepitant; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Granisetron hydrochloride	N/A

Detailed Description

OBJECTIVES:

Primary

• Evaluate the efficacy of the addition of aprepitant in controlling acute vomiting with the standard prophylactic anti-emetic combination of granisetron hydrochloride and dexamethasone in patients receiving therapy comprising high-dose cyclophosphamide to mobilize stem cells prior to leukapheresis for autologous stem cell transplantation.

Secondary

• Evaluate the efficacy of the addition of aprepitant in controlling delayed vomiting in these patients.

• Evaluate the efficacy of the addition of aprepitant in controlling overall nausea in these patients.

• Identify side effects of the addition of aprepitant to this regimen in these patients.

OUTLINE: Patients receive granisetron hydrochloride orally or IV and oral dexamethasone, followed 1 hour later by cyclophosphamide IV over 2 hours on day 1. Patients also receive oral aprepitant once daily on days 1-3. Treatment continues in absence of unacceptable toxicity.

After completion of study treatment, patients are followed for 30 days.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Pilot Study Evaluating Aprepitant (MK-869) for Prevention of Nausea & Vomiting Secondary to High Dose Cyclophosphamide Administered to Patients Underging Undergoing Peripheral Hematopoietic Progenitor Cell Mobilization Prior to Autologous Transplantation
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Aprepitant, Dexamethasone, Cytoxan & Kytril Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning.

Drug: Aprepitant; Aprepitant 80mg once daily in the morning on days 2 and 3; Other Names: Emend ; Drug: Cyclophosphamide; Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes; Other Names: Cytoxan® Neosar® ; Drug: Dexamethasone; Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration.; Other Names: Decadron Diodex Hexadrol Maxidex Dexamethasone Sodium Phosphate Dexamethasone Acetate ; Drug: Granisetron hydrochloride; Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.; Other Names: KYTRIL®

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Controlled Acute Vomiting [at 0-24 hours]

   No episodes of vomiting and no rescue medication during first 24 hours after cyclophosphamide administration.

Secondary Outcome Measures

1. Delayed Vomiting Controlled [at 25-120 hours]

2. Toxicity Grade 3, 4, or 5 [at 0-120 hours]

Other Outcome Measures

1. Overall Nausea Controlled [at 0-120 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Undergoing autologous peripheral blood stem cell transplantation and stem cell mobilization using cyclophosphamide

• Candidate (per institutional requirements) for autologous peripheral blood stem cell transplantation

• No psychiatric illness or multi-system organ failure

• No nausea at baseline

PATIENT CHARACTERISTICS:

• SWOG performance status 0-2

• Fewer than 5 alcoholic drinks per day within the past year

• No current illness requiring chronic systemic steroids or requirement for chronic use of anti-emetics

• No gastrointestinal obstruction or active peptic ulcer disease

• AST and ALT ≤ 3 times upper limit of normal (ULN)

• Bilirubin ≤ 3 times ULN

• Alkaline phosphatase ≤ 3 times ULN

• Creatinine ≤ 2 mg/dL

• No known hypersensitivity to any component of the study regimen

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• No unrelenting hiccups

PRIOR CONCURRENT THERAPY:

• No chronic therapeutic warfarin > 1 mg dose per day

• No other concurrent investigational agents

• No concurrent oral contraceptives (except for stopping menses), tolbutamide, phenytoin, midazolam, ketoconazole, rifampin, paroxetine hydrochloride, or diltiazem hydrochloride

• No concurrent illegal drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379

Sponsors and Collaborators

• Barbara Ann Karmanos Cancer Institute
• National Cancer Institute (NCI)

Investigators

• Study Chair: Muneer H. Abidi, MD, Barbara Ann Karmanos Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Muneer Abidi, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT00293384
• Other Study ID Numbers: CDR0000456201; P30CA022453; WSU-D-2797; WSU-0504001728
• First Posted: Feb 17, 2006
• Last Update Posted: Mar 15, 2016
• Last Verified: Feb 1, 2016

• Keywords provided by Muneer Abidi, Principal Investigator, Barbara Ann Karmanos Cancer Institute: nausea and vomiting; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; atypical chronic myeloid leukemia, BCR-ABL negative; blastic phase chronic myelogenous leukemia; chronic eosinophilic leukemia; primary myelofibrosis; chronic myelomonocytic leukemia; chronic neutrophilic leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; disseminated neuroblastoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; myelodysplastic/myeloproliferative neoplasm, unclassifiable; nodal marginal zone B-cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; poor prognosis metastatic gestational trophoblastic tumor; previously treated myelodysplastic syndromes; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; recurrent adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent neuroblastoma; recurrent ovarian epithelial cancer; recurrent ovarian germ cell tumor; recurrent small lymphocytic lymphoma; recurrent malignant testicular germ cell tumor; refractory chronic lymphocytic leukemia; refractory hairy cell leukemia; refractory multiple myeloma; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; splenic marginal zone lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage II ovarian epithelial cancer; stage III adult Burkitt lymphoma; stage III adult Hodgkin lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III chronic lymphocytic leukemia; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III multiple myeloma; stage III ovarian epithelial cancer; stage III small lymphocytic lymphoma; stage III malignant testicular germ cell tumor; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV adult Burkitt lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV breast cancer; stage IV chronic lymphocytic leukemia; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV ovarian epithelial cancer; stage IV small lymphocytic lymphoma
• Additional relevant MeSH terms: Lymphoma; Breast Neoplasms; Neoplasms; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Neuroblastoma; Neoplasms, Germ Cell and Embryonal; Plasmacytoma; Trophoblastic Neoplasms; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Nausea; Vomiting; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Aprepitant; Granisetron; Dexamethasone 21-phosphate; BB 1101

Study Results

Participant Flow

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Period Title: Overall Study
STARTED	40
COMPLETED	35
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Overall Participants	40
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	40 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	17 42.5%
Male	23 57.5%
Region of Enrollment (participants) [Number]
United States	40 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Controlled Acute Vomiting
Description	No episodes of vomiting and no rescue medication during first 24 hours after cyclophosphamide administration.
Time Frame	at 0-24 hours

Outcome Measure Data

Analysis Population Description

Evaluable for response

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Measure Participants	35
Number [participants]	20 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aprepitant, Dexamethasone, Cytoxan & Kytril
	Comments	Optimal Simon design for phase II study. p0=45% p1=65%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments	85% statistical power
	Method	Simon optimal design
	Comments
Method of Estimation	Estimation Parameter	proportion
	Estimated Value	.57
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Delayed Vomiting Controlled
Time Frame	at 25-120 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Measure Participants	35
Number [participants]	22 55%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aprepitant, Dexamethasone, Cytoxan & Kytril
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion
	Estimated Value	0.63
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	Overall Nausea Controlled
Time Frame	at 0-120 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Measure Participants	35
Number [participants]	31 77.5%

4. Secondary Outcome

Title	Toxicity Grade 3, 4, or 5
Time Frame	at 0-120 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
Measure Participants	35
Number [participants]	2 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aprepitant, Dexamethasone, Cytoxan & Kytril
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion
	Estimated Value	0.06
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Aprepitant, Dexamethasone, Cytoxan & Kytril
Arm/Group Description	Day 1: 1 mg of Kytril orally or I.V., 10 mg of Dexamethasone orally, and Aprepitant 125 mg orally, 1 hour prior to cyclophosphamide administration. Cyclophosphamide 4gm/m2 I.V. over 90 - 120 minutes. Days 2 & 3: Aprepitant 80 mg once daily in the morning. Aprepitant: Aprepitant 80mg once daily in the morning on days 2 and 3 Cyclophosphamide: Cyclophosphamide 4 gm/m2 I.V. over 90-120 minutes Dexamethasone: Dexamethasone orally 10 mg 1 hour prior to cyclophosphamide administration. Granisetron hydrochloride: Kytril 1 mg orally or I.V., 1 hour prior to cyclophosphamide administration.
All Cause Mortality
	Aprepitant, Dexamethasone, Cytoxan & Kytril
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aprepitant, Dexamethasone, Cytoxan & Kytril
	Affected / at Risk (%)	# Events
Total	10/35 (28.6%)
Blood and lymphatic system disorders
Febrile Neutropenia	6/35 (17.1%)	6
Gastrointestinal disorders
Diarrhea	1/35 (2.9%)	1
Vomiting	2/35 (5.7%)	2
General disorders
Pain	1/35 (2.9%)
Infections and infestations
Infection	2/35 (5.7%)	3
Metabolism and nutrition disorders
Hypokalemia	1/35 (2.9%)	2
Hypophosphatemia	1/35 (2.9%)	2
Mucositis	1/35 (2.9%)	1
Musculoskeletal and connective tissue disorders
Musculokeletal Pain	1/35 (2.9%)	1
Renal and urinary disorders
Hydronephrosis	1/35 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Aprepitant, Dexamethasone, Cytoxan & Kytril
	Affected / at Risk (%)	# Events
Total	33/35 (94.3%)
Cardiac disorders
Tachycardia	3/35 (8.6%)	3
Gastrointestinal disorders
Nausea	24/35 (68.6%)	47
Diarrhea	10/35 (28.6%)	12
Vomiting	14/35 (40%)	16
Constipation	4/35 (11.4%)	4
Belching	2/35 (5.7%)	2
Acid Refulx	2/35 (5.7%)	2
Mucositis	2/35 (5.7%)	2
General disorders
Fever	6/35 (17.1%)	6
Pain- Cath site	2/35 (5.7%)	2
Fatigue	17/35 (48.6%)	22
Infections and infestations
Infection	2/35 (5.7%)	2
Investigations
Weight gain	2/35 (5.7%)	3
Metabolism and nutrition disorders
Hypokalemia	15/35 (42.9%)	19
Hypophosphatemia	5/35 (14.3%)	5
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	7/35 (20%)	8
Nervous system disorders
Headache	7/35 (20%)	8
Neuropathy	3/35 (8.6%)	3
Lightheaded	2/35 (5.7%)	2
Drowsy	2/35 (5.7%)	2
Psychiatric disorders
Insomnia	3/35 (8.6%)	3
Respiratory, thoracic and mediastinal disorders
Hiccups	7/35 (20%)	7
Skin and subcutaneous tissue disorders
Rash	3/35 (8.6%)	3

Limitations/Caveats

There were no other significant limitations except for the details provided.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.