Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT01132807
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 164
• Locations: 95
• Arm: 1
• Duration (Months): 92.1
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well chemotherapy based on positron emission tomography (PET) scan works in treating patients with stage I or stage II Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started. Comparing results of diagnostic procedures, such as PET scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: Bleomycin Sulfate; Drug: Doxorubicin Hydrochloride; Drug: Procarbazine Hydrochloride; Drug: Vinblastine Sulfate; Drug: Dacarbazine; Drug: Cyclophosphamide; Drug: Etoposide phosphate; Drug: prednisone; Drug: Radiation Therapy; Radiation: Fludeoxyglucose F-18; Procedure: computed tomography; Procedure: Positron Emission Tomography	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the progression-free survival (PFS) from enrollment for patients with non-bulky stage I and II Hodgkin lymphoma.

2. To compare the PFS of patients who are PET positive versus PET negative following 2 cycles of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).

SECONDARY OBJECTIVES:

1. To evaluate the complete response (CR) rate of patients diagnosed with non-bulky stage I and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation therapy.

2. To determine the predictive value of fludeoxyglucose (FDG) uptake using various semi-quantitative approaches, at baseline, after 2 cycles of AVBD and at completion of therapy.

3. To determine the predictive value of volumetric changes on computed tomography (CT) vs 2-dimensional (2-D) analyses after 2 cycles and 4 cycles and compare with PET parameters with and without combination analyses (PET + dedicated CT data).

4. To compare the predictive value of metabolic parameters/changes that are measured both visually and semi-quantitatively, International Harmonization Project (IHP) criteria, 2-D and volumetric CT changes, molecular parameters, and conventional parameters, including International Prognostic Score (IPS).

5. To assess whether elevated baseline circulating markers of inflammation (including soluble cluster of differentiation CD30 [sCD]30, soluble CD 163 [CD163], interleukin-10 (IL10), chemokine (C-C motif) ligand 17 (CCL17), and chemokine (C-C motif) ligand 22 [CCL22]) correlate with clinical response and PFS and PET scan results.

6. To assess whether persistent or recurrent elevated serial circulating markers of inflammation (including soluble CD30 [sCD30], soluble CD163 [sCD163], IL10, CCL17, or CCL22) correlate with relapse/progression or PET scan results.

7. To confirm independently useful tissue biomarkers for risk stratification in patients with non-bulky stage I and II Hodgkin lymphoma treated with this regimen.

8. To compare mediastinal bulk on standing posterior-anterior (PA) and lateral chest x-ray (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

OUTLINE:

ABVD CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 3-5 minutes, bleomycin sulfate IV over 3-5 minutes, vinblastine IV over 3-5 minutes, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 2 courses. Patients then undergo PET scan. Patients achieving complete response (CR), partial response (PR), or stable disease (SD) with a negative PET scan receive 2 additional courses of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity. Patients achieving CR, PR, or SD with a positive PET scan proceed to escalated BEACOPP chemotherapy.

ESCALATED BEACOPP* CHEMOTHERAPY: Patients receive doxorubicin hydrochloride IV over 3-5 minutes and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 45-60 minutes on days 1-3, procarbazine orally (PO) on days 1-7, prednisone PO on days 1-14, and bleomycin sulfate IV and vincristine IV on day 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after completion of BEACOPP chemotherapy, patients undergo involved-field radiotherapy (IFRT) 5 days a week for 3½ weeks.

NOTE: * HIV-positive patients receive standard BEACOPP instead of escalated BEACOPP.

Patients undergo fludeoxyglucose F^18 PET/CT scan at baseline, and within 8-10 days after completion of chemotherapy. Patients also undergo additional PET/CT scans within 3-4 weeks after completion of ABVD or within 12 weeks after completion of BEACOPP and IFRT. Patients with a negative PET scan proceed to follow up. Patients with a positive PET scan undergo biopsy**. Patients with a negative biopsy proceed to follow up, and patients with a positive biopsy are treated at the discretion of the investigator.

NOTE: ** Patients for whom biopsy is neither clinically appropriate nor medically feasible proceed to follow-up. Patients for whom biopsy is neither clinically indicated nor medically appropriate undergo a repeat PET/CT scan after 3 months. If PET/CT scan remains positive, patients undergo biopsy as above.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 2-3 years, and then annually for a maximum of 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 164 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Response-Adapted Chemotherapy Based on Positron Emission Tomography for Non-Bulky Stage I and II Hodgkin Lymphoma
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemotherapy and F-18 PET/CT) See Detailed Description

Biological: Bleomycin Sulfate; Given IV; Drug: Doxorubicin Hydrochloride; Given IV; Drug: Procarbazine Hydrochloride; Given PO; Drug: Vinblastine Sulfate; Given IV; Drug: Dacarbazine; Given IV; Drug: Cyclophosphamide; Given IV; Drug: Etoposide phosphate; Given IV; Drug: prednisone; Given PO; Drug: Radiation Therapy; Undergo radiation therapy; Radiation: Fludeoxyglucose F-18; Undergo FDG PET/CT; Procedure: computed tomography; Undergo FDG PET/CT; Procedure: Positron Emission Tomography; Undergo FDG PET/CT

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) at 36-Months for Patients Who Received 4 Cycles of ABVD [36 Months]

   The primary objective of this trial is to estimate the 3 year PFS in patients who received 4 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, all patients that received 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) are included.

2. 36 Month Progression Free Survival Rate of Patients Receiving 4 Cycles of ABVD Versus Patients Receiving 2 Cycles of ABVD and 2 Cycles of BEACOPP and Radiation. [at 36 months]

   All patients received an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15. After the first 2 cycles of ABVD, PET/CT was performed and submitted for central review (cycle 2, days 23-25) and determined whether patients would receive 2 cycles of escalated BEACOPP and involved-field RT (IFRT) or an additional 2 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS rate at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, we compare the PFS rate between patients who received 4 cycles of ABVD and patients who received 2 cycles of ABVD and 2 cycles of IFRT.

Secondary Outcome Measures

1. Complete Response Rate [Up to 5 years]

   A Complete Response (CR) was defined as having the following conditions: 1. A complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. In patients with a PET scan that was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET-negative. A Complete Response rate was defined as the number of patients who achieved a CR divided by the number of patients that were eligible for analysis in each group. The CR rate was calculated for patients that completed 4 cycles of ABVD and for patients that completed 2 cycles of ABVD and 2 cycles of BEACOPP and IFRT.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed* Hodgkin lymphoma

• Clinical stage IA, IB, IIA, or IIB disease according to the modified Ann Arbor Staging Classification system

• Subclassified according to the WHO modification of the Rye Classification

• "E" extension allowed provided all other criteria have been met NOTE: *Pathology materials must be submitted within 60 days of study registration. Core-needle biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping. Fine-needle aspirates not allowed. If multiple specimens are available, submit the most recent.

• No nodular lymphocyte-predominant Hodgkin lymphoma

• No mediastinal mass > 0.33 maximum intrathoracic diameter by standing postero-anterior chest x-ray or peripheral or retroperitoneal adenopathy > 10 cm in its largest diameter

• Measurable disease by physical examination or imaging studies

• Any tumor mass measurable in two dimensions and > 1 cm (or 1.5 cm if 0.5 cm slices are used, as in spiral CT scans) allowed

• Lesions that are considered intrinsically non-measurable include:

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Lesions that are situated in a previously irradiated area

PATIENT CHARACTERISTICS:

• Performance status 0-2

• ANC ≥ 1,000/μL

• Platelet count ≥ 100,000/μL

• Serum creatinine ≤ 2 mg/dL

• Bilirubin ≤ 2 mg/dL

• AST ≤ 2 times upper limit of normal

• LVEF normal by ECHO or MUGA

• DLCO ≥ 60% with no symptomatic pulmonary disease

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Patients with known HIV allowed provided they have CD4 counts ≥ 350/mcL

• Patients must not have multi-drug resistant HIV infections (i.e., concurrent AIDS-defining conditions)

• An HIV test is required for patients with a history of IV drug abuse or any behavior associated with an increased risk of HIVinfection

• No "currently active" second malignancy other than nonmelanoma skin cancers

• Patients are not considered to have a "currently active" malignancy provided they have completed therapy and are considered by their physician to be at < 30% risk of relapse

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy or radiotherapy for Hodgkin lymphoma

• 1 course of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) allowed and will be considered the first course

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
3	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
4	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
5	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
6	M.D. Anderson Cancer Center at Orlando	Orlando	Florida	United States	32806
7	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
8	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii	United States	96701
9	Oncare Hawaii, Incorporated - Pali Momi	'Aiea	Hawaii	United States	96701
10	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii	United States	96813
11	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii	United States	96813
12	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii	United States	96813
13	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii	United States	96817-3169
14	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
15	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
16	Castle Medical Center	Kailua	Hawaii	United States	96734
17	Kauai Medical Clinic	Lihue	Hawaii	United States	96766
18	Mount Sinai Hospital Medical Center	Chicago	Illinois	United States	60608
19	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
20	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-3785
21	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
22	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
23	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
24	Evanston Hospital	Evanston	Illinois	United States	60201-1781
25	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
26	McFarland Clinic, PC	Ames	Iowa	United States	50010
27	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
28	CCOP - Wichita	Wichita	Kansas	United States	67214
29	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
30	Louisville Oncology at Norton Cancer Institute - Louisville	Louisville	Kentucky	United States	40202
31	Norton Suburban Hospital	Louisville	Kentucky	United States	40207
32	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
33	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
34	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana	United States	70112
35	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine	United States	04401
36	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
37	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
38	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
39	Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
40	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts	United States	01655
41	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
42	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
43	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
44	CCOP - Duluth	Duluth	Minnesota	United States	55805
45	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
46	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
47	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
48	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
49	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
50	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
51	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
52	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
53	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York	United States	11042
54	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
55	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
56	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
57	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
58	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
59	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
60	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
61	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
62	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
63	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
64	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
65	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
66	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
67	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
68	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
69	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
70	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
71	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
72	Fox Chase Cancer Center CCOP Research Base	Philadelphia	Pennsylvania	United States	19140
73	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
74	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
75	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
76	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
77	West Tennessee Cancer Center at Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
78	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
79	Harrington Cancer Center	Amarillo	Texas	United States	79106
80	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
81	Mountainview Medical	Berlin	Vermont	United States	05602
82	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
83	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
84	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
85	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
86	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
87	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
88	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
89	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
90	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
91	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
92	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
93	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
94	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin	United States	54481
95	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David J. Straus, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT01132807
• Other Study ID Numbers: CALGB-50604; CALGB-50604; NCI-2011-02042; U10CA180821; CDR0000672913
• First Posted: May 28, 2010
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Alliance for Clinical Trials in Oncology: stage I adult Hodgkin lymphoma; stage II adult Hodgkin lymphoma
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Prednisone; Cyclophosphamide; Dacarbazine; Doxorubicin; Liposomal doxorubicin; Etoposide; Bleomycin; Vinblastine; Etoposide phosphate; Procarbazine; Fluorodeoxyglucose F18

Study Results

Participant Flow

Pre-assignment Detail	Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. PET/CT central review occurred after cycle 2. PET-negative patients received 2 additional cycles of ABVD. PET-positive patients received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP.

Arm/Group Title	Only Initial ABVD Treatment	Treatment (ABVD:Additional 2 Cycles)	Escalated BEACOPP and Involved Field Radiation Therapy
Arm/Group Description	Therapy consisted of 2 initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.> Doxorubicin 25 mg/m2 IV on Days 1 and 15> Bleomycin 10 units/m2 IV on Days 1 and 15> Vinblastine 6 mg/m2 IV on Days 1 and 15> Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15	Therapy consisted of an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.> Doxorubicin 25 mg/m2 IV on Days 1 and 15> Bleomycin 10 units/m2 IV on Days 1 and 15> Vinblastine 6 mg/m2 IV on Days 1 and 15> Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15> Patients underwent a PET/CT central review (cycle 2, days 23-25) and received an additional 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle.	Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. > Doxorubicin 25 mg/m2 IV on Days 1 and 15> Bleomycin 10 units/m2 IV on Days 1 and 15> Vinblastine 6 mg/m2 IV on Days 1 and 15> Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15> >> > >> Patients underwent a PET/CT central review (cycle 2, days 23-25) and received an additional 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP:> >> > >> Bleomycin 10 units/m2 IV on Day 8> >> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 > >> Doxorubicin 35 mg/m2 IV on Day 1 > >> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 > >> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 > >> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Period Title: Initial ABVD Treatment (2 Cycles)
STARTED	15	135	14
COMPLETED	0	135	14
NOT COMPLETED	15	0	0
Period Title: Initial ABVD Treatment (2 Cycles)
STARTED	0	135	14
COMPLETED	0	135	14
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Treatment (ABVD x2 Cycles)
Arm/Group Description	Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days.>> Doxorubicin 25 mg/m2 IV on Days 1 and 15>> Bleomycin 10 units/m2 IV on Days 1 and 15>> Vinblastine 6 mg/m2 IV on Days 1 and 15>> Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15>> >> PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD. >> >> Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP:>> Bleomycin 10 units/m2 IV on Day 8>> Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 >> Doxorubicin 35 mg/m2 IV on Day 1 >> Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 >> Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 >> Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7>> Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Overall Participants	164
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	31
Sex: Female, Male (Count of Participants)
Female	76 46.3%
Male	88 53.7%
Region of Enrollment (participants) [Number]
United States	164 100%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) at 36-Months for Patients Who Received 4 Cycles of ABVD
Description	The primary objective of this trial is to estimate the 3 year PFS in patients who received 4 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, all patients that received 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) are included.
Time Frame	36 Months

Outcome Measure Data

Analysis Population Description

All patients that received 4 cycles of ABVD were included in this analysis

Arm/Group Title	Treatment (ABVD: 4 Cycles)
Arm/Group Description	Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.
Measure Participants	135
Number (95% Confidence Interval) [proportion of patients]	.91

2. Primary Outcome

Title	36 Month Progression Free Survival Rate of Patients Receiving 4 Cycles of ABVD Versus Patients Receiving 2 Cycles of ABVD and 2 Cycles of BEACOPP and Radiation.
Description	All patients received an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15. After the first 2 cycles of ABVD, PET/CT was performed and submitted for central review (cycle 2, days 23-25) and determined whether patients would receive 2 cycles of escalated BEACOPP and involved-field RT (IFRT) or an additional 2 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS rate at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, we compare the PFS rate between patients who received 4 cycles of ABVD and patients who received 2 cycles of ABVD and 2 cycles of IFRT.
Time Frame	at 36 months

Outcome Measure Data

Analysis Population Description

All patients that completed an initial 2 cycles of ABVD were included in this endpoint.

Arm/Group Title	Treatment (ABVD:4 Cycles)	Escalated BEACOPP and Involved Field Radiation Therapy
Arm/Group Description	Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: > > Bleomycin 10 units/m2 IV on Day 8 > Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 > Doxorubicin 35 mg/m2 IV on Day 1 > Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 > Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 > Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 > Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Measure Participants	135	14
Number (95% Confidence Interval) [proportion of participants]	.91 0.6%	.67 NaN

3. Secondary Outcome

Title	Complete Response Rate
Description	A Complete Response (CR) was defined as having the following conditions: 1. A complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. In patients with a PET scan that was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET-negative. A Complete Response rate was defined as the number of patients who achieved a CR divided by the number of patients that were eligible for analysis in each group. The CR rate was calculated for patients that completed 4 cycles of ABVD and for patients that completed 2 cycles of ABVD and 2 cycles of BEACOPP and IFRT.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

Two patients began a third cycle of ABVD and were not eligible for response evaluation (one withdrew and one was lost to follow up). Fourteen patients started BEACOPP treatment, and one patient was lost to follow-up and not included in this analysis.

Arm/Group Title	Treatment (ABVD: 4 Cycles)	Escalated BEACOPP and Involved Field Radiation Therapy
Arm/Group Description	Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.	Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: > > Bleomycin 10 units/m2 IV on Day 8 > Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 > Doxorubicin 35 mg/m2 IV on Day 1 > Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 > Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 > Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 > Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
Measure Participants	133	13
Number (95% Confidence Interval) [proportion of participants]	.97 0.6%	.85 NaN

Adverse Events

Time Frame	Adverse events were collected after every cycle of treatment up to 4 -28 day cycles.
Arm/Group Title	Only Initial Treatment (ABVD x2 Cycles)		Treatment (ABVD:4 Cycles)		Escalated BEACOPP and Involved Field Radiation Therapy
Arm/Group Description	Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14		Therapy consisted of 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with a negative PET/CT (Deauville 1, 2, or 3) received 2 additional cycles of ABVD.		Therapy consisted of 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15 of each cycle. A cycle is 28 days. Doxorubicin 25 mg/m2 IV on Days 1 and 15 Bleomycin 10 units/m2 IV on Days 1 and 15 Vinblastine 6 mg/m2 IV on Days 1 and 15 Dacarbazine 375 mg/m2 IV infusion on Days 1 and 15 PET/CT central review (cycle 2, days 23-25). Patients with positive PET received 2-21 day cycles of 3060-cGy involved-field RT (IFRT) and escalated BEACOPP: Bleomycin 10 units/m2 IV on Day 8 Etoposide 200 mg/m2 IV over 60 minutes on Days 1, 2 and 3 Doxorubicin 35 mg/m2 IV on Day 1 Cyclophosphamide 1250 mg/m2 IV over 60 minutes on Day 1 Vincristine 1.4 mg/m2 (maximum 2 mg) IV on Day 8 Procarbazine 100 mg/m2 (rounded to nearest 50 mg) orally on Days 1-7 Prednisone 40 mg/m2 (rounded to nearest 5 mg) orally on Days 1-14
All Cause Mortality
	Only Initial Treatment (ABVD x2 Cycles)		Treatment (ABVD:4 Cycles)		Escalated BEACOPP and Involved Field Radiation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/135 (0%)		0/14 (0%)
Serious Adverse Events
	Only Initial Treatment (ABVD x2 Cycles)		Treatment (ABVD:4 Cycles)		Escalated BEACOPP and Involved Field Radiation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		12/135 (8.9%)		2/14 (14.3%)
Blood and lymphatic system disorders
Anemia	1/15 (6.7%)	2	5/135 (3.7%)	5	1/14 (7.1%)	1
Febrile neutropenia	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Cardiac disorders
Chest pain - cardiac	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Myocardial infarction	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Constipation	1/15 (6.7%)	1	4/135 (3%)	4	0/14 (0%)	0
Diarrhea	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Dyspepsia	1/15 (6.7%)	2	1/135 (0.7%)	1	0/14 (0%)	0
Mucositis oral	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Nausea	1/15 (6.7%)	1	8/135 (5.9%)	8	0/14 (0%)	0
Vomiting	1/15 (6.7%)	1	2/135 (1.5%)	2	0/14 (0%)	0
General disorders
Chills	1/15 (6.7%)	1	1/135 (0.7%)	1	0/14 (0%)	0
Fatigue	1/15 (6.7%)	2	5/135 (3.7%)	5	0/14 (0%)	0
Fever	1/15 (6.7%)	1	1/135 (0.7%)	1	0/14 (0%)	0
Pain	1/15 (6.7%)	1	0/135 (0%)	0	0/14 (0%)	0
Infections and infestations
Sepsis	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Skin infection	1/15 (6.7%)	1	1/135 (0.7%)	1	0/14 (0%)	0
Soft tissue infection	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Investigations
Alanine aminotransferase increased	1/15 (6.7%)	2	3/135 (2.2%)	3	0/14 (0%)	0
Alkaline phosphatase increased	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Aspartate aminotransferase increased	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
CD4 lymphocytes decreased	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
CO diffusing capacity decreased	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Ejection fraction decreased	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Lymphocyte count increased	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Neutrophil count decreased	1/15 (6.7%)	2	8/135 (5.9%)	8	2/14 (14.3%)	2
Platelet count decreased	1/15 (6.7%)	1	1/135 (0.7%)	1	1/14 (7.1%)	1
White blood cell decreased	1/15 (6.7%)	2	7/135 (5.2%)	7	2/14 (14.3%)	2
Metabolism and nutrition disorders
Anorexia	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Dehydration	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Hyperglycemia	1/15 (6.7%)	2	2/135 (1.5%)	2	0/14 (0%)	0
Hyperuricemia	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Hypocalcemia	1/15 (6.7%)	2	0/135 (0%)	0	0/14 (0%)	0
Hypoglycemia	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Hypokalemia	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Hyponatremia	1/15 (6.7%)	1	1/135 (0.7%)	1	1/14 (7.1%)	1
Musculoskeletal and connective tissue disorders
Bone pain	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Myalgia	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Nervous system disorders
Dizziness	1/15 (6.7%)	2	0/135 (0%)	0	0/14 (0%)	0
Headache	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Peripheral motor neuropathy	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Peripheral sensory neuropathy	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Psychiatric disorders
Anxiety	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Depression	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Insomnia	1/15 (6.7%)	1	0/135 (0%)	0	0/14 (0%)	0
Reproductive system and breast disorders
Irregular menstruation	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Cough	0/15 (0%)	0	3/135 (2.2%)	3	1/14 (7.1%)	1
Dyspnea	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Nasal congestion	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Bullous dermatitis	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Hyperhidrosis	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Rash acneiform	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Skin ulceration	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Vascular disorders
Thromboembolic event	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Only Initial Treatment (ABVD x2 Cycles)		Treatment (ABVD:4 Cycles)		Escalated BEACOPP and Involved Field Radiation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/15 (53.3%)		131/135 (97%)		13/14 (92.9%)
Blood and lymphatic system disorders
Anemia	2/15 (13.3%)	2	66/135 (48.9%)	169	7/14 (50%)	16
Febrile neutropenia	0/15 (0%)	0	7/135 (5.2%)	7	1/14 (7.1%)	1
Hemolysis	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Leukocytosis	0/15 (0%)	0	1/135 (0.7%)	1	1/14 (7.1%)	1
Cardiac disorders
Chest pain - cardiac	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Left ventricular systolic dysfunction	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Palpitations	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	3
Paroxysmal atrial tachycardia	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Sinus tachycardia	0/15 (0%)	0	3/135 (2.2%)	4	0/14 (0%)	0
Ear and labyrinth disorders
Ear pain	0/15 (0%)	0	3/135 (2.2%)	3	1/14 (7.1%)	1
External ear pain	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Tinnitus	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Vertigo	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Vestibular disorder	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Eye disorders
Blurred vision	0/15 (0%)	0	4/135 (3%)	5	1/14 (7.1%)	3
Dry eye	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Eye disorders - Other, specify	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Eye pain	1/15 (6.7%)	1	1/135 (0.7%)	1	0/14 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/15 (0%)	0	11/135 (8.1%)	18	0/14 (0%)	0
Anal mucositis	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Anal pain	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Bloating	0/15 (0%)	0	2/135 (1.5%)	4	0/14 (0%)	0
Constipation	4/15 (26.7%)	5	69/135 (51.1%)	134	5/14 (35.7%)	9
Diarrhea	0/15 (0%)	0	19/135 (14.1%)	28	1/14 (7.1%)	1
Dry mouth	0/15 (0%)	0	1/135 (0.7%)	3	1/14 (7.1%)	2
Dyspepsia	0/15 (0%)	0	17/135 (12.6%)	28	4/14 (28.6%)	5
Dysphagia	0/15 (0%)	0	1/135 (0.7%)	1	1/14 (7.1%)	1
Esophagitis	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Flatulence	0/15 (0%)	0	2/135 (1.5%)	4	0/14 (0%)	0
Gastric perforation	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Gastritis	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Gastroesophageal reflux disease	0/15 (0%)	0	4/135 (3%)	5	0/14 (0%)	0
Gastrointestinal disorders - Oth spec	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Gastrointestinal pain	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Gingival pain	1/15 (6.7%)	1	1/135 (0.7%)	1	1/14 (7.1%)	1
Hemorrhoidal hemorrhage	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Hemorrhoids	1/15 (6.7%)	1	0/135 (0%)	0	0/14 (0%)	0
Mucositis oral	0/15 (0%)	0	29/135 (21.5%)	45	7/14 (50%)	11
Nausea	4/15 (26.7%)	9	111/135 (82.2%)	288	10/14 (71.4%)	31
Oral dysesthesia	0/15 (0%)	0	2/135 (1.5%)	3	0/14 (0%)	0
Oral pain	0/15 (0%)	0	6/135 (4.4%)	8	0/14 (0%)	0
Rectal hemorrhage	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Rectal pain	0/15 (0%)	0	2/135 (1.5%)	5	1/14 (7.1%)	2
Stomach pain	0/15 (0%)	0	4/135 (3%)	6	1/14 (7.1%)	1
Toothache	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Vomiting	2/15 (13.3%)	3	46/135 (34.1%)	72	5/14 (35.7%)	9
General disorders
Chills	0/15 (0%)	0	5/135 (3.7%)	8	3/14 (21.4%)	4
Edema face	1/15 (6.7%)	1	1/135 (0.7%)	1	0/14 (0%)	0
Edema limbs	0/15 (0%)	0	9/135 (6.7%)	16	1/14 (7.1%)	1
Fatigue	5/15 (33.3%)	10	92/135 (68.1%)	235	9/14 (64.3%)	23
Fever	0/15 (0%)	0	17/135 (12.6%)	23	3/14 (21.4%)	4
Flu like symptoms	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Gait disturbance	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Gen disord and admin site conds-Oth spec	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Infusion site extravasation	0/15 (0%)	0	3/135 (2.2%)	4	0/14 (0%)	0
Injection site reaction	0/15 (0%)	0	6/135 (4.4%)	9	0/14 (0%)	0
Localized edema	0/15 (0%)	0	2/135 (1.5%)	2	1/14 (7.1%)	1
Malaise	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Non-cardiac chest pain	0/15 (0%)	0	9/135 (6.7%)	14	3/14 (21.4%)	4
Pain	1/15 (6.7%)	1	10/135 (7.4%)	13	2/14 (14.3%)	2
Immune system disorders
Allergic reaction	0/15 (0%)	0	3/135 (2.2%)	3	1/14 (7.1%)	1
Infections and infestations
Anorectal infection	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Bronchial infection	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Conjunctivitis	0/0 (NaN)	0	1/135 (0.7%)	1	0/14 (0%)	0
Infections and infestations - Oth spec	1/15 (6.7%)	1	3/135 (2.2%)	3	1/14 (7.1%)	1
Kidney infection	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Lymph gland infection	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Mucosal infection	0/15 (0%)	0	2/135 (1.5%)	3	1/14 (7.1%)	1
Nail infection	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Otitis media	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Papulopustular rash	0/15 (0%)	0	2/135 (1.5%)	3	0/14 (0%)	0
Pharyngitis	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Phlebitis infective	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Rhinitis infective	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Sinusitis	0/15 (0%)	0	2/135 (1.5%)	3	1/14 (7.1%)	1
Skin infection	0/15 (0%)	0	4/135 (3%)	5	0/14 (0%)	0
Upper respiratory infection	0/15 (0%)	0	9/135 (6.7%)	9	1/14 (7.1%)	1
Urinary tract infection	0/15 (0%)	0	3/135 (2.2%)	3	1/14 (7.1%)	2
Injury, poisoning and procedural complications
Bruising	0/15 (0%)	0	2/135 (1.5%)	2	1/14 (7.1%)	1
Inj, pois and proced complic - Oth spec	0/15 (0%)	0	1/135 (0.7%)	4	0/14 (0%)	0
Investigations
Activated partial throm time prolonged	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Alanine aminotransferase increased	1/15 (6.7%)	1	36/135 (26.7%)	81	6/14 (42.9%)	8
Alkaline phosphatase increased	1/15 (6.7%)	1	7/135 (5.2%)	10	0/14 (0%)	0
Aspartate aminotransferase increased	0/15 (0%)	0	29/135 (21.5%)	57	4/14 (28.6%)	5
Blood bilirubin increased	0/15 (0%)	0	3/135 (2.2%)	4	1/14 (7.1%)	1
CD4 lymphocytes decreased	0/15 (0%)	0	4/135 (3%)	4	0/14 (0%)	0
CO diffusing capacity decreased	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Cholesterol high	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Creatinine increased	1/15 (6.7%)	1	3/135 (2.2%)	3	0/14 (0%)	0
Hemoglobin increased	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
INR increased	0/15 (0%)	0	2/135 (1.5%)	4	0/14 (0%)	0
Investigations - Other, specify	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Lymphocyte count decreased	1/15 (6.7%)	4	28/135 (20.7%)	53	5/14 (35.7%)	10
Lymphocyte count increased	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Neutrophil count decreased	6/15 (40%)	11	113/135 (83.7%)	337	9/14 (64.3%)	24
Platelet count decreased	2/15 (13.3%)	2	9/135 (6.7%)	10	8/14 (57.1%)	10
Weight gain	0/15 (0%)	0	8/135 (5.9%)	14	0/14 (0%)	0
Weight loss	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
White blood cell decreased	6/15 (40%)	11	112/135 (83%)	334	12/14 (85.7%)	33
Metabolism and nutrition disorders
Anorexia	0/15 (0%)	0	19/135 (14.1%)	35	3/14 (21.4%)	7
Dehydration	0/15 (0%)	0	3/135 (2.2%)	4	0/14 (0%)	0
Glucose intolerance	0/15 (0%)	0	2/135 (1.5%)	3	0/14 (0%)	0
Hypercalcemia	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Hyperglycemia	0/15 (0%)	0	40/135 (29.6%)	95	3/14 (21.4%)	4
Hyperkalemia	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Hypernatremia	0/15 (0%)	0	4/135 (3%)	4	0/14 (0%)	0
Hypertriglyceridemia	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Hypoalbuminemia	0/15 (0%)	0	17/135 (12.6%)	27	2/14 (14.3%)	3
Hypocalcemia	0/15 (0%)	0	12/135 (8.9%)	19	2/14 (14.3%)	2
Hypoglycemia	1/15 (6.7%)	1	4/135 (3%)	7	0/14 (0%)	0
Hypokalemia	0/15 (0%)	0	12/135 (8.9%)	24	4/14 (28.6%)	6
Hypomagnesemia	0/15 (0%)	0	2/135 (1.5%)	3	0/14 (0%)	0
Hyponatremia	0/15 (0%)	0	14/135 (10.4%)	18	1/14 (7.1%)	1
Hypophosphatemia	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Metabolism, nutrition disord - Oth spec	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/15 (6.7%)	1	15/135 (11.1%)	24	4/14 (28.6%)	5
Arthritis	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Back pain	2/15 (13.3%)	2	11/135 (8.1%)	13	2/14 (14.3%)	6
Bone pain	1/15 (6.7%)	1	7/135 (5.2%)	10	2/14 (14.3%)	2
Chest wall pain	0/15 (0%)	0	4/135 (3%)	5	0/14 (0%)	0
Flank pain	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Generalized muscle weakness	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Joint range of motion decreased	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Muscle weakness lower limb	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Muscle weakness upper limb	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Musculoskeletal, conn tissue - Oth spec	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Myalgia	1/15 (6.7%)	1	21/135 (15.6%)	44	2/14 (14.3%)	6
Myositis	1/15 (6.7%)	1	0/135 (0%)	0	0/14 (0%)	0
Neck pain	0/15 (0%)	0	5/135 (3.7%)	5	1/14 (7.1%)	1
Pain in extremity	0/15 (0%)	0	19/135 (14.1%)	39	1/14 (7.1%)	1
Trismus	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Nervous system disorders
Cognitive disturbance	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Dizziness	0/15 (0%)	0	15/135 (11.1%)	19	1/14 (7.1%)	1
Dysgeusia	0/15 (0%)	0	9/135 (6.7%)	23	1/14 (7.1%)	1
Headache	0/15 (0%)	0	26/135 (19.3%)	37	6/14 (42.9%)	12
Memory impairment	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Movements involuntary	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Nervous system disorders - Oth spec	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Neuralgia	0/15 (0%)	0	3/135 (2.2%)	4	0/14 (0%)	0
Olfactory nerve disorder	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Paresthesia	0/15 (0%)	0	1/135 (0.7%)	2	1/14 (7.1%)	1
Peripheral motor neuropathy	0/15 (0%)	0	4/135 (3%)	6	1/14 (7.1%)	1
Peripheral sensory neuropathy	2/15 (13.3%)	4	57/135 (42.2%)	121	5/14 (35.7%)	10
Presyncope	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Somnolence	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Tremor	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Vasovagal reaction	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Psychiatric disorders
Agitation	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Anxiety	2/15 (13.3%)	4	23/135 (17%)	43	4/14 (28.6%)	9
Depression	0/15 (0%)	0	7/135 (5.2%)	17	0/14 (0%)	0
Insomnia	2/15 (13.3%)	2	18/135 (13.3%)	39	6/14 (42.9%)	11
Irritability	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Renal and urinary disorders
Urinary frequency	0/15 (0%)	0	1/135 (0.7%)	1	1/14 (7.1%)	2
Urinary incontinence	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	1
Urinary retention	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Urinary tract pain	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Reproductive system and breast disorders
Irregular menstruation	0/15 (0%)	0	1/135 (0.7%)	2	1/14 (7.1%)	1
Pelvic pain	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Testicular pain	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/15 (0%)	0	7/135 (5.2%)	9	1/14 (7.1%)	1
Cough	2/15 (13.3%)	3	44/135 (32.6%)	66	4/14 (28.6%)	7
Dyspnea	0/15 (0%)	0	38/135 (28.1%)	66	2/14 (14.3%)	3
Epistaxis	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Hiccups	1/15 (6.7%)	1	3/135 (2.2%)	4	0/14 (0%)	0
Hoarseness	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Hypoxia	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Laryngeal inflammation	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Nasal congestion	0/15 (0%)	0	9/135 (6.7%)	13	1/14 (7.1%)	1
Pharyngolaryngeal pain	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Pleuritic pain	0/15 (0%)	0	1/135 (0.7%)	2	0/14 (0%)	0
Pneumonitis	0/15 (0%)	0	2/135 (1.5%)	2	0/14 (0%)	0
Postnasal drip	0/15 (0%)	0	2/135 (1.5%)	3	0/14 (0%)	0
Sinus pain	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Sore throat	0/15 (0%)	0	8/135 (5.9%)	11	1/14 (7.1%)	1
Wheezing	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	3/15 (20%)	3	47/135 (34.8%)	99	3/14 (21.4%)	5
Bullous dermatitis	0/15 (0%)	0	2/135 (1.5%)	3	0/14 (0%)	0
Dry skin	1/15 (6.7%)	1	3/135 (2.2%)	3	2/14 (14.3%)	2
Erythema multiforme	0/15 (0%)	0	0/135 (0%)	0	1/14 (7.1%)	2
Hyperhidrosis	0/15 (0%)	0	1/135 (0.7%)	2	1/14 (7.1%)	1
Nail discoloration	0/15 (0%)	0	4/135 (3%)	6	1/14 (7.1%)	1
Pain of skin	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Palmar-plantar erythrodysesthesia syndrm	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Photosensitivity	0/15 (0%)	0	1/135 (0.7%)	3	0/14 (0%)	0
Pruritus	1/15 (6.7%)	1	15/135 (11.1%)	23	3/14 (21.4%)	4
Rash acneiform	0/15 (0%)	0	3/135 (2.2%)	3	0/14 (0%)	0
Rash maculo-papular	0/15 (0%)	0	17/135 (12.6%)	30	1/14 (7.1%)	2
Skin and subcut tissue disord - Oth spec	0/15 (0%)	0	4/135 (3%)	5	4/14 (28.6%)	5
Skin hyperpigmentation	2/15 (13.3%)	2	9/135 (6.7%)	12	1/14 (7.1%)	1
Urticaria	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Vascular disorders
Flushing	1/15 (6.7%)	1	2/135 (1.5%)	5	0/14 (0%)	0
Hot flashes	0/15 (0%)	0	7/135 (5.2%)	9	0/14 (0%)	0
Hypertension	0/15 (0%)	0	3/135 (2.2%)	4	0/14 (0%)	0
Hypotension	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Lymphedema	0/15 (0%)	0	1/135 (0.7%)	1	0/14 (0%)	0
Phlebitis	0/15 (0%)	0	4/135 (3%)	5	1/14 (7.1%)	2
Thromboembolic event	0/15 (0%)	0	4/135 (3%)	7	2/14 (14.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.