Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00290498
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 67
• Location: 1
• Arms: 2
• Actual Duration (Months): 144.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The overall goal of this clinical research study was to find out which of two different chemotherapy drug combinations, R-CHOP and R-HCVAD, is more effective in treating B-cell lymphoma.

At this point, all participants will now be assigned to the R-HCVAD arm of the study. Researchers will study the safety and effectiveness of this drug combination.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Dexamethasone; Drug: Methotrexate; Drug: Cytarabine; Drug: Prednisone	Phase 2

Detailed Description

This study originally involved 2 different study drug regimens, R-CHOP and R-HCVAD. R-CHOP is made up of rituximab, cyclophosphamide, vincristine, and prednisone, and is the most common treatment for patients with non-Hodgkin's lymphoma. This combination was compared with R-HCVAD, which is made up of rituximab, doxorubicin, cyclophosphamide, vincristine, and dexamethasone.

Rituximab (Rituxan®) is a humanized monoclonal antibody against cluster of differentiation antigen 20 (CD20) (a receptor in the surface of malignant B-cell lymphocytes). The drug has activity against aggressive and nonaggressive NHL of B-cell origin, and has been used in combination with chemotherapy. Cyclophosphamide is a type of drug know as an alkylating agent. Vincristine is a type of drug called vinca alkaloids. It is typically used in lymphomas, leukemias, and other tumors. Prednisone is a type of steroid. Dexamethasone is a steroid that may have activity against lymphomas. Methotrexate is an anti-cancer drug and a folic acid antagonist. It is used to treat solid tumors, lymphomas, leukemias, and autoimmune diseases.

When this study began, participants were randomly assigned (as in the flip of a coin) to 1 of 2 arms: Arm A (R-HCVAD alternating with a combination of rituximab, methotrexate, and Ara-C) or Arm B (R-CHOP). From this point on, all new participants will be treated with the Arm A combination, which has shown to be better.

If you are found to be eligible to take part in this study, you will be given the study drugs in 21-day cycles. The cycles will alternate between R-HCVAD and a combination of rituximab, methotrexate, and Ara-C. During Cycle 1 (the R-HCVAD cycle), you will receive rituximab through a needle in your vein (intravenously, or "IV"), on Day 1. The infusion will take about 1 hour. Cyclophosphamide will be given by IV every 12 hours for 3 days. Each infusion of cyclophosphamide will take about 3 hours. Doxorubicin will be given as a 15-minute infusion on Day 5 with the supervision of a nurse. Your doctor may also choose to give you the doxorubicin over 24-48 hours using a small pump that you will carry around your waist in a "fanny pack." You will not have to stay in the hospital to receive this study drug. Vincristine will be given by IV, on Days 5 and 12. Each vincristine infusion will take about an hour. Dexamethasone will be given by mouth (as a pill, capsule, or tablet) on Days 2-5 and 12-15. You will also be given other standard medications to help prevent possible side effects of these medications (such as nausea, vomiting, or rash).

In Cycle 2 (the rituximab-methotrexate-Ara-C cycle), you will receive rituximab on Day 1. You will receive methotrexate by IV (after finishing the rituximab) on Days 2 and 3. The infusion will take about 24 hours. You will be given a small "fanny pack" with a pump inside that will slowly infuse the drug. You do not have to stay in the hospital while the drug is being given. You will be given Ara-C every 12 hours on Days 3-4 (a total of 4 doses). You will be given other standard medications to help prevent possible side effects of these medications (such as nausea, vomiting, or rash) during this cycle also.

Leucovorin is given 12 hours after each methotrexate infusion. It is used to stop the action of the methotrexate and to prevent/lessen any side effects that the methotrexate may cause.

During treatment, you will have blood draws (between 2-3 tablespoons) every week for routine tests. Every 4 weeks during treatment , you will be asked questions about your medical history and have a physical exam to check for any side effects. Every 2 cycles (about every 8 weeks), you will have bone marrow biopsies performed (if they were positive before starting on this study), until they come back negative. You will have a positron emission tomography (PET) scan to see if the tumor is responding. Once the PET scan comes back negative, it will be up to your physician to decide if you need additional PET scan tests, and when. You will have CT scans of the chest, abdomen, pelvis, and neck every 2 cycles, if they were positive at the beginning of the study also. You may have additional testing done while on this study, if your physician feels that it is needed (for example, if it is needed to check for side effects).

You may receive additional medication called "CNS prophylaxis" before receiving the study treatments. Your doctor will discuss these medications with you. The "CNS prophylaxis" consists of an alternating dose of either doxorubicin or methotrexate. The methotrexate will be given either by IV pump or by a "lumbar puncture" (a needle inserted into the space between the vertebrae in your back to infuse the drug directly into the spinal area). The doxorubicin will be given by IV. Changes in the dose level of CNS prophylaxis will be approved if you are at risk for or are experiencing serious side effects.

You will receive the study drugs for up to 6-8 cycles on an outpatient basis. This means you will not have to be admitted to the hospital to receive the study drugs. You may be taken off study if the disease gets worse. If you experience intolerable side effects while taking any of the study drugs, your study doctor may decide to delay your treatment for up to 3 weeks (one study cycle) or to continue your therapy on the drugs at a lower dose. If the side effects become very severe, your doctor may decide to take you off of the study and stop the medication.

At the end of your scheduled treatments, you will be asked to return to the clinic for follow-up visits every 6 months for the first, second, third, and fourth year after treatment on this study. You will then be followed every year after that. If your doctor feels it is necessary, you may have blood tests (about 3-5 teaspoons) performed at these visits. You will have bone marrow biopsies every other year for the first 2 years, if they were positive before you started on this study, and then every year after that. At these visits, you will be asked about any side effects you may have experienced and whether or not your cancer has come back. If your doctor feels there is a chance that the cancer has come back, he or she may schedule x-rays or scans in order to check. You will also be asked about any other therapies you may be having to treat your cancer, if it has come back.

If you are taken off study for any reason, you will be asked to come back to the clinic for an end-of-treatment visit within 4 weeks from the last treatment. This visit will include a physical exam, routine blood tests (about 5-8 teaspoons), a blood-pregnancy test for women who are able to get pregnant, an ECG, and a chest x-ray.

This is an investigational study. All of the study drugs are approved by the FDA for the treatment of lymphoma. Up to 66 patients will take part in this study. All of the patients will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger
• Actual Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Aug 11, 2017
• Actual Study Completion Date: Aug 11, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A R-HCVAD + R-MTX/Ara-C ((Rituximab-HCVAD (rituximab, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) alternating with Rituximab-Methotrexate-Cytarabine))	Drug: Rituximab; Arm A: Rituximab 375 mg/m² by vein on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles.; Other Names: Rituxan ; Drug: Cyclophosphamide; Arm A: Cyclophosphamide 300 mg/m^2 by vein (IVPB) over 3 hours every 12 hours x 6 doses on Days 2-4, Cycle 1 and alternating cycles. Arm B: Cyclophosphamide 750 mg/m² by vein day 1; Other Names: Cytoxan Neosar ; Drug: Doxorubicin; Arm A: Doxorubicin 50 mg/m^2/day by vein over 15 minutes (12 hours after last dose of cyclophosphamide) on Day 5, Cycle 1 and alternating cycles.; Other Names: AD Hydroxydaunomycin hydrochloride ; Drug: Vincristine; Arm A: Vincristine 1.4 mg/m^2 (maximum 2 mg) by vein (IVPB) on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles. Arm B: Vincristine 1.4 mg/m^2 (maximum 2 mg) by vein (IVPB) on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle.; Drug: Dexamethasone; Arm A: Dexamethasone 40 mg by vein or by mouth daily x 4 on Days 2-5 and on days 12-15 of cycle 1 and alternating cycles.; Other Names: Decadron ; Drug: Methotrexate; Arm A: Methotrexate after finishing Rituximab, 200 mg/m2 by vein over 2 hours, then 800 mg/m2 by vein over 22 hours day 1 cycle 2.
Active Comparator: Arm B R-CHOP ((Rituximab-CHOP (Rituximab, cyclophosphamide, vincristine, and prednisone)) No longer recruiting for this study arm.	Drug: Rituximab; Arm A: Rituximab 375 mg/m² by vein on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles.; Other Names: Rituxan ; Drug: Cyclophosphamide; Arm A: Cyclophosphamide 300 mg/m^2 by vein (IVPB) over 3 hours every 12 hours x 6 doses on Days 2-4, Cycle 1 and alternating cycles. Arm B: Cyclophosphamide 750 mg/m² by vein day 1; Other Names: Cytoxan Neosar ; Drug: Cytarabine; Arm B: Cytarabine 3 g/m^2 by vein over 2 hours every 12 hours X 4 doses on days 3 & 4, cycle 2 and alternating cycles.; Other Names: Ara-C Cytosar DepoCyt Cytosine arabinosine hydrochloride ; Drug: Prednisone; Arm B: Prednisone 100 mg by mouth (as a pill, capsule, or tablet) once a day on Days 1-5, each cycle.

Outcome Measures

Primary Outcome Measures

1. Response Rate R-HCVAD vs. R-CHOP [3 years]

   Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Progression Free Survival (Rate) [3 years post-therapy]

   Progression free survival (PFS) for three years following therapy with Rituxan-HCVAD alternating with Rituximab with high -dose methotrexate/ara-C and standard R-CHOP in patients with newly diagnosed B-cell aggressive non-Hodgkin's lymphomas younger than 60 years old and with adjusted IPI 2 or higher adverse prognostic features.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Confirmed diagnosis of previously untreated large B-cell Non Hodgkin's, Large Cell Lymphoma and B-Cell with high grade features. Other aggressive lymphomas such as Primary Mediastinal large B-cell Lymphomas will be also allowed to be included.

2. Patients with performance status of 0-2 (Zubrod Scale).

3. Serum bilirubin <1.5 mg/dl and serum creatinine < 2.0 mg/dl unless due to lymphoma; absolute neutrophil count (ANC) >1000/mm^{3 and platelets >100,000/mm}3 unless due to lymphoma.

4. Cardiac ejection fraction 50% or greater.

5. Ages 16 - 60 years (due to the fact that CHOP-R is not studied enough in younger patients and is not considered standard of care).

6. Patients must be willing to receive transfusions of blood products.

7. Age adjusted International Prognostic Index Score of 2 or more

8. Previous steroids are allowed (if used to relieve some symptoms such as SVC, etc).

Exclusion Criteria:

1. Pregnancy (excluded due to the teratogenicity of the involved chemotherapy agents

2. Positive HIV serology because of poor tolerance to this intense chemotherapy regimen

3. Burkitt's lymphomas, and Mantle cell lymphoma, transformed follicular center cell lymphoma, follicular grade III.

4. Any clinical or cytological diagnosis of central nervous system (CNS) involvement

5. Any co-morbid medical, such as Child's Class C liver cirrhosis, end-stage renal disease, and symptomatic congestive heart failure, or psychiatric illnesses that preclude treatment with intense dose chemotherapy as determined by the primary investigator.

6. Concurrent or previous malignancy whose prognosis is poor (< 90% probability of survival at 5 years)

7. Active Hepatitis B or C. Chronic carriers for Hepatitis B will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Genentech, Inc.

Investigators

• Principal Investigator: Luis E. Fayad, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 17, 2012

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00290498
• Other Study ID Numbers: 2005-0054; NCI-2012-01355
• First Posted: Feb 13, 2006
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Non-Hodgkin's Lymphoma; B-Cell Non-Hodgkin's Lymphoma; Lymphoma; Cyclophosphamide; Cytarabine; Doxorubicin; Hyper-CVAD; Methotrexate; Prednisone; Rituximab; Vincristine; R-CHOP; R-HCVAD; Dexamethasone; Decadron; Leucovorin; Ara-C; Cytosar; Cytoxan; DepoCyt; Cytosine arabinosine hydrochloride; AD; Hydroxydaunomycin hydrochloride; Neosar
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Cytarabine; Dexamethasone; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine

Study Results

Participant Flow

Recruitment Details	Patient eligibility:>/16 -</60 years old and untreated Diffuse Large B-cell Lymphoma,stage II >/10cm mass or stage III/IV),Eastern Cooperative Oncology Group 0-2,age-adjusted Integrated Pulmonary Index of .2, and adequate organ function. Excluded:if they were pregnant,breast-feeding,or evidenced central nervous system lymphoma or active infections.
Pre-assignment Detail	Three participants were screen failures. Eight participants were removed

Arm/Group Title	R-HCVAD-MA	R-CHOP
Arm/Group Description	I.V. rituximab 375mg, cyclophosphamide 300mg, doxorubicin 50mg & vincristine 1.4mg - 2mg, & oral dexamethasone 40mg. Alternate R-MA: IV rituximab 375mg, methotrexate 200mg & 800mg 22h, & cytarabine 3g.	R-CHOP: Day 1 I.V. rituximab 375mg, cyclophosphamide 750mg, doxorubicin 50mg, vincristine 1.4mg max 2mg, and oral prednisone 100mg orally.
Period Title: Overall Study
STARTED	49	10
COMPLETED	41	10
NOT COMPLETED	8	0

Baseline Characteristics

Arm/Group Title	R-HCVAD/R-MA	R-CHOP	Total
Arm/Group Description	I.V. rituximab 375mg, cyclophosphamide 300mg, doxorubicin 50mg & vincristine 1.4mg - 2mg, & oral dexamethasone 40mg. Alternate R-MA: IV rituximab 375mg, methotrexate 200mg & 800mg 22h, & cytarabine 3g.	R-CHOP: Day 1 I.V. rituximab 375mg, cyclophosphamide 750mg, doxorubicin 50mg, vincristine 1.4mg max 2mg, and oral prednisone 100mg orally.	Total of all reporting groups
Overall Participants	49	10	59
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	49 100%	10 100%	59 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (11)	39 (11)	42.5 (22)
Sex: Female, Male (Count of Participants)
Female	15 30.6%	5 50%	20 33.9%
Male	34 69.4%	5 50%	39 66.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 8.2%	1 10%	5 8.5%
Not Hispanic or Latino	45 91.8%	9 90%	54 91.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 4.1%	0 0%	2 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 14.3%	0 0%	7 11.9%
White	40 81.6%	10 100%	50 84.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	49 100%	10 100%	59 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate R-HCVAD vs. R-CHOP
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	R-HCVAD	R-CHOP
Arm/Group Description	I.V. rituximab 375mg, cyclophosphamide 300mg, doxorubicin 50mg & vincristine 1.4mg - 2mg, & oral dexamethasone 40mg. Alternate R-MA: IV rituximab 375mg, methotrexate 200mg & 800mg 22h, & cytarabine 3g.	R-CHOP: Day 1 I.V. rituximab 375mg, cyclophosphamide 750mg, doxorubicin 50mg, vincristine 1.4mg max 2mg, and oral prednisone 100mg orally.
Measure Participants	49	10
Complete Remission	40 81.6%	7 70%
Inevaluable	2 4.1%	1 10%
Progressive Disease	1 2%	1 10%
Partial Remission	4 8.2%	0 0%
Complete Remission Unconfirmed	2 4.1%	1 10%

2. Secondary Outcome

Title	Progression Free Survival (Rate)
Description	Progression free survival (PFS) for three years following therapy with Rituxan-HCVAD alternating with Rituximab with high -dose methotrexate/ara-C and standard R-CHOP in patients with newly diagnosed B-cell aggressive non-Hodgkin's lymphomas younger than 60 years old and with adjusted IPI 2 or higher adverse prognostic features.
Time Frame	3 years post-therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	R-HCVAD/MA	R-CHOP
Arm/Group Description	I.V. rituximab 375mg, cyclophosphamide 300mg, doxorubicin 50mg & vincristine 1.4mg - 2mg, & oral dexamethasone 40mg. Alternate R-MA: IV rituximab 375mg, methotrexate 200mg & 800mg 22h, & cytarabine 3g.	R-CHOP: Day 1 I.V. rituximab 375mg, cyclophosphamide 750mg, doxorubicin 50mg, vincristine 1.4mg max 2mg, and oral prednisone 100mg orally.
Measure Participants	49	10
Count of Participants [Participants]	35 71.4%	7 70%

Adverse Events

Time Frame	From the initiation of the regimen until the end of chemotherapy, an average of 3 years
Arm/Group Title	RHCVAD		RCHOP
Arm/Group Description	Rituximab 375mg/m2 intravenously on day 1,cyclophosphamide 300mg/m2 intravenously every 12 h for six doses on days 13,doxorubicin 50mg/m2 intravenously on day 5,vincristine 1.4mg/m2 or maximum 2mg intravenously on days 5 and 12,and dexamethasone 40mg intravenously or orally on days 25,alternating with RMA(cycles 2,4,6,)rituximab 375mg/2 intravenously on day 1,methotrexate 200mg/m2 over 2 h followed by 800mg/m2 over 22 h on day 1, and cytarabine 3g/m2 every 12 h for four doses on days 3 and 4, with a 21 day cycle.		RCHOP consisted of rituximab 375mg/m2 intravenously on day 1,cyclophosphamide 750mg/m2 intravenously on day 1,doxorubicin 50mg/m2 intravenously on day 1 either over 15min or 48 h , vincristine 1.4mg/m2 or maximum 2mg intravenously,and prednisone 100mg orally on days 15,with a 21d cycle.
All Cause Mortality
	RHCVAD		RCHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/49 (8.2%)		0/10 (0%)
Serious Adverse Events
	RHCVAD		RCHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/49 (100%)		7/10 (70%)
Blood and lymphatic system disorders
BLOOD BONE MARROW (OTHER)	1/49 (2%)		0/10 (0%)
FEBRILE NEUTROPENIA	27/49 (55.1%)		2/10 (20%)
HEMORRHAGE	8/49 (16.3%)		1/10 (10%)
PETECHIAE	6/49 (12.2%)		0/10 (0%)
PHLEBITIS	1/49 (2%)		0/10 (0%)
Cardiac disorders
ATRIAL FIBRILLATION	1/49 (2%)		0/10 (0%)
ATRIAL FLUTTER	2/49 (4.1%)		0/10 (0%)
HYPERTENSION	9/49 (18.4%)		0/10 (0%)
HYPOTENSION	13/49 (26.5%)		0/10 (0%)
PALPITATIONS	1/49 (2%)		1/10 (10%)
PERICARDIAL EFFUSION	1/49 (2%)		1/10 (10%)
SINUS BRADYCARDIA	3/49 (6.1%)		0/10 (0%)
SINUS TACHYCARDIA	9/49 (18.4%)		0/10 (0%)
TACHYCARDIA	2/49 (4.1%)		1/10 (10%)
Ear and labyrinth disorders
AUDITORY/EAR (OTHER)	1/49 (2%)		0/10 (0%)
TINNITUS	4/49 (8.2%)		0/10 (0%)
Endocrine disorders
ENDOCRINE (OTHER)	1/49 (2%)		0/10 (0%)
HYPERTHYROIDISM	1/49 (2%)		0/10 (0%)
HYPOTHYROIDISM	1/49 (2%)		0/10 (0%)
Eye disorders
BLURRED VISION	0/49 (0%)		2/10 (20%)
DRY EYE	2/49 (4.1%)		0/10 (0%)
OCULAR/VISUAL(OTHER)	1/49 (2%)		0/10 (0%)
PAIN (EYE)	1/49 (2%)		0/10 (0%)
WATERY EYE	4/49 (8.2%)		2/10 (20%)
Gastrointestinal disorders
ABDOMINAL CRAMPING	1/49 (2%)		1/10 (10%)
CONSTIPATION	16/49 (32.7%)		0/10 (0%)
DIARRHEA	11/49 (22.4%)		2/10 (20%)
DISTENSION/BLOATING	1/49 (2%)		0/10 (0%)
DRY MOUTH	2/49 (4.1%)		1/10 (10%)
DYSPHAGIA	2/49 (4.1%)		0/10 (0%)
GASTRITIS	7/49 (14.3%)		0/10 (0%)
GERD	2/49 (4.1%)		0/10 (0%)
GASTROINTESTINAL (OTHER)	2/49 (4.1%)		1/10 (10%)
HEARTBURN	5/49 (10.2%)		0/10 (0%)
HEMORRHOIDS	6/49 (12.2%)		0/10 (0%)
NAUSEA	30/49 (61.2%)		6/10 (60%)
OBSTRUCTION,GI	2/49 (4.1%)		0/10 (0%)
PAIN (ABDOMEN NOS)	6/49 (12.2%)		2/10 (20%)
PAIN (ANUS)	0/49 (0%)		1/10 (10%)
PAIN( ORALCAVITY)	1/49 (2%)		0/10 (0%)
PAIN( STOMACH)	1/49 (2%)		0/10 (0%)
STOMATITIS	3/49 (6.1%)		2/10 (20%)
TASTE ALTERATION	2/49 (4.1%)		0/10 (0%)
TEETH	2/49 (4.1%)		0/10 (0%)
VOMITING	24/49 (49%)		5/10 (50%)
General disorders
DEATH NOS	2/49 (4.1%)		0/10 (0%)
DRUG FEVER	1/49 (2%)		0/10 (0%)
EDEMA	8/49 (16.3%)		3/10 (30%)
EDEMA:HEAD AND NECK	2/49 (4.1%)		0/10 (0%)
EDEMA:LIMB	13/49 (26.5%)		3/10 (30%)
EDEMA:TRUNK/GENITAL	2/49 (4.1%)		0/10 (0%)
EDEMA (LARYNX)	1/49 (2%)		0/10 (0%)
FATIGUE	31/49 (63.3%)		2/10 (20%)
FEVER UNKNOWN ORIGIN	2/49 (4.1%)		1/10 (10%)
FEVER WITHOUT NEUTROPENI	14/49 (28.6%)		3/10 (30%)
FLU-LIKE SYNDROME	1/49 (2%)		1/10 (10%)
GAIT/WALKING	1/49 (2%)		0/10 (0%)
PAIN (DENTAL/TEETH/PERID	2/49 (4.1%)		1/10 (10%)
PAIN (NOS)	4/49 (8.2%)		2/10 (20%)
RIGORS/CHILLS	18/49 (36.7%)		1/10 (10%)
Immune system disorders
ALLERGIC REACTION DRUG	10/49 (20.4%)		1/10 (10%)
ALLERGY (OTHER)	1/49 (2%)		1/10 (10%)
AUTOIMMUNE REACTION	1/49 (2%)		0/10 (0%)
Infections and infestations
CANDIDIASIS	3/49 (6.1%)		0/10 (0%)
INFECTION(S)	47/49 (95.9%)		6/10 (60%)
Injury, poisoning and procedural complications
BRUISING (NON-THROMBOPENIA)	1/49 (2%)		0/10 (0%)
Investigations
ALKALINE PHOSPHATASE INCR	4/49 (8.2%)		1/10 (10%)
ALT,SGPT INCR	17/49 (34.7%)		3/10 (30%)
AST,SGOT INCR	17/49 (34.7%)		1/10 (10%)
BILIRUBIN INCREASE	9/49 (18.4%)		0/10 (0%)
CHOLESTEROL,SERUM-HIGH	1/49 (2%)		0/10 (0%)
CREATININE INCREASE	7/49 (14.3%)		2/10 (20%)
ELEV LDH (OTHER)	6/49 (12.2%)		3/10 (30%)
GRANULOCYTOPENIA	0/49 (0%)		1/10 (10%)
HEMOGLOBIN DECREASE	48/49 (98%)		7/10 (70%)
HYPERGLYCEMIA	25/49 (51%)		6/10 (60%)
HYPERKALEMIA	2/49 (4.1%)		0/10 (0%)
HYPERURICEMIA	4/49 (8.2%)		5/10 (50%)
HYPOALBUMINEMIA	27/49 (55.1%)		4/10 (40%)
HYPOCALCEMIA	15/49 (30.6%)		4/10 (40%)
HYPOGLYCEMIA	1/49 (2%)		1/10 (10%)
HYPOKALEMIA	15/49 (30.6%)		4/10 (40%)
HYPOMAGNESEMIA	14/49 (28.6%)		6/10 (60%)
HYPONATREMIA	7/49 (14.3%)		2/10 (20%)
HYPOPHOSPHATEMIA	2/49 (4.1%)		0/10 (0%)
LEUKOPENIA	48/49 (98%)		7/10 (70%)
NEUTROPENIA	46/49 (93.9%)		4/10 (40%)
OLIGURIA	1/49 (2%)		0/10 (0%)
PLATELETS DECREASED	39/49 (79.6%)		3/10 (30%)
THROMBOCYTOPENIA	7/49 (14.3%)		1/10 (10%)
Metabolism and nutrition disorders
ANOREXIA	1/49 (2%)		1/10 (10%)
DEHYDRATION	2/49 (4.1%)		0/10 (0%)
DIABETES	3/49 (6.1%)		0/10 (0%)
METABOLIC/LABORATORY (OTHER)	1/49 (2%)		1/10 (10%)
OBESITY	2/49 (4.1%)		0/10 (0%)
WEIGHT GAIN	1/49 (2%)		1/10 (10%)
WEIGHT LOSS	1/49 (2%)		1/10 (10%)
Musculoskeletal and connective tissue disorders
MUSCLE WEAKNESS	8/49 (16.3%)		1/10 (10%)
MYALGIA	3/49 (6.1%)		0/10 (0%)
MYOSITIS	1/49 (2%)		0/10 (0%)
PAIN (BACK)	10/49 (20.4%)		1/10 (10%)
PAIN (BONE)	5/49 (10.2%)		1/10 (10%)
PAIN (EXTREMITY-LIMB)	6/49 (12.2%)		0/10 (0%)
PAIN (JOINT)	3/49 (6.1%)		0/10 (0%)
PAIN (MUSCLE)	7/49 (14.3%)		2/10 (20%)
PAIN (NECK)	5/49 (10.2%)		0/10 (0%)
PAIN (PELVIS)	1/49 (2%)		0/10 (0%)
Nervous system disorders
COGNITIVE DISTURBANCE	1/49 (2%)		0/10 (0%)
DIZZINESS	14/49 (28.6%)		3/10 (30%)
HEADACHE	1/49 (2%)		0/10 (0%)
MEMORY IMPAIRMENT	1/49 (2%)		0/10 (0%)
NEUROPATHY:MOTOR	1/49 (2%)		3/10 (30%)
NEUROPATHY:SENSORY	20/49 (40.8%)		4/10 (40%)
PAIN( HEAD/HEADACHE)	22/49 (44.9%)		3/10 (30%)
PAIN (NEURALGIA/PERIPHERALNER	1/49 (2%)		0/10 (0%)
SENSORY	2/49 (4.1%)		1/10 (10%)
SYNCOPE (FAINTING)	7/49 (14.3%)		0/10 (0%)
Psychiatric disorders
CONFUSION	1/49 (2%)		0/10 (0%)
INSOMNIA	12/49 (24.5%)		2/10 (20%)
MOOD ALTERATION	16/49 (32.7%)		2/10 (20%)
Renal and urinary disorders
DYSURIA	1/49 (2%)		1/10 (10%)
HEMATURIA	1/49 (2%)		0/10 (0%)
POLYURIA	1/49 (2%)		0/10 (0%)
RENAL FAILURE	4/49 (8.2%)		0/10 (0%)
URINARY FREQUENCY	1/49 (2%)		1/10 (10%)
Reproductive system and breast disorders
HOT FLASHES	1/49 (2%)		0/10 (0%)
MENORRHAGIA	1/49 (2%)		0/10 (0%)
PAIN (BREAST)	1/49 (2%)		0/10 (0%)
PAIN (TESTICLE)	2/49 (4.1%)		0/10 (0%)
PAIN (VAGINA)	1/49 (2%)		0/10 (0%)
VAGINAL DRYNESS	1/49 (2%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS	9/49 (18.4%)		3/10 (30%)
COUGH	17/49 (34.7%)		4/10 (40%)
DYSPNEA	22/49 (44.9%)		3/10 (30%)
HEMOPTYSIS	1/49 (2%)		1/10 (10%)
HORSENESS	0/49 (0%)		1/10 (10%)
HYPOXIA	1/49 (2%)		1/10 (10%)
MUCOSITIS	20/49 (40.8%)		3/10 (30%)
PAIN (CHEST/THORAX)	7/49 (14.3%)		0/10 (0%)
PAIN (PLEURITIC)	0/49 (0%)		1/10 (10%)
PAIN (THROAT/PHARYNX/LARYNX)	3/49 (6.1%)		0/10 (0%)
PLEURAL EFFUSION	8/49 (16.3%)		0/10 (0%)
PNEUMONITIS	1/49 (2%)		0/10 (0%)
PNEUMOTHORAX	1/49 (2%)		0/10 (0%)
PULMONARY(OTHER)	1/49 (2%)		1/10 (10%)
RESPIRATORY FAILURE	1/49 (2%)		0/10 (0%)
RHINORRHEA	6/49 (12.2%)		0/10 (0%)
SORE THROAT	1/49 (2%)		0/10 (0%)
UPPER RESPIRATORY INFECT	1/49 (2%)		0/10 (0%)
VOICE CHANGES	3/49 (6.1%)		1/10 (10%)
Skin and subcutaneous tissue disorders
ALOPECIA	20/49 (40.8%)		5/10 (50%)
DERMATOLOGY/SKIN (OTHER)	1/49 (2%)		0/10 (0%)
DRY SKIN	3/49 (6.1%)		0/10 (0%)
ERYTHEMA MULTIFORME	5/49 (10.2%)		0/10 (0%)
HAND-FOOT SYNDROME	4/49 (8.2%)		0/10 (0%)
HYPERPIGMENTATION	1/49 (2%)		0/10 (0%)
PRURITUS	4/49 (8.2%)		0/10 (0%)
PRURITUS/ITCHING	1/49 (2%)		0/10 (0%)
PULMONARY EMBOLISM	1/49 (2%)		0/10 (0%)
RASH/DESQUAMATION	14/49 (28.6%)		2/10 (20%)
SWEATING	7/49 (14.3%)		1/10 (10%)
ULCERATION	1/49 (2%)		0/10 (0%)
Vascular disorders
FLUSHING	4/49 (8.2%)		0/10 (0%)
HEMATOMA	0/49 (0%)		1/10 (10%)
SYNDROMES (OTHER)	1/49 (2%)		0/10 (0%)
THROMBOSIS/THROMBUS/EMBOLISM	12/49 (24.5%)		1/10 (10%)
VASCULAR (OTHER)	1/49 (2%)		1/10 (10%)
Other (Not Including Serious) Adverse Events
	RHCVAD		RCHOP
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/49 (93.9%)		8/10 (80%)
Blood and lymphatic system disorders
Neutrophils	46/49 (93.9%)		4/10 (40%)
Platelets	39/49 (79.6%)		3/10 (30%)
Infections and infestations
Febrile Neutropenia	25/49 (51%)		2/10 (20%)
Infection	33/49 (67.3%)		5/10 (50%)
Renal and urinary disorders
Renal Failure	4/49 (8.2%)		0/10 (0%)
Vascular disorders
Thrombosis/Embolism	12/49 (24.5%)		1/10 (10%)

Limitations/Caveats

[Not Specified]

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.