Chemotherapy Plus Ofatumumab Followed by G-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01329900
• Collaborator: Novartis (Industry)
• Enrollment: 50
• Location: 1
• Arm: 1
• Actual Duration (Months): 94.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if it is possible to collect stem cells after ofatumumab and chemotherapy treatment. This study will also evaluate side-effects, number of stem cells collected, and the number of procedures that are needed to collect enough stem cells.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: Ofatumumab; Drug: Ifosfamide; Drug: Etoposide; Drug: Mesna; Drug: G-CSF; Procedure: Stem Cell Collection	Phase 2

Detailed Description

The Study Drugs:

Ofatumumab is a human monoclonal antibody for the CD20 protein designed to bind to the surface of some of the white blood cells (B-cells). It can destroy cancer cells that come from B-cells, and can be used to treat cancers of B-cells such as resistant CLL (chronic lymphocytic leukemia).

Etoposide is designed to slow or stop the growth of cancer cells.

Filgrastim promotes the growth of white blood cells, which help to fight infections.

Ifosfamide is designed to slow or stop the growth of cancer cells.

Mesna is a drug that protects bladder cells from damage by the chemotherapy drug ifosfamide. It is used to decrease the risk of bleeding in the bladder.

Treatment Administration:

You will be admitted to the hospital. You will have to stay in the hospital for 4-6 days for this part of the treatment.

On Day 1, you will receive ofatumumab through the CVL over 6-8 hours.

On Days 2, 3, and 4, you will receive ifosfamide and mesna continuously and etoposide every 12 hours. Mesna is given to help decrease the risk of developing side effects.

As an outpatient, you will receive a higher dose of ofatumumab (about 1 week after the first one) through the CVL over 10-12 hours.

Beginning on Day 6, you will get G-CSF (filgrastim) injections (given under the skin) and will continue to be given until enough stem cells have been collected.

Tests and Procedures:

Every day while you are in the hospital, you will have a physical exam and you will be asked about any side effects you may be having. After you are no longer in the hospital, you will have a physical exam and you will be asked about any side effects you may be having when the doctor thinks it is needed.

While you are waiting for enough stem cells to be collected, you will have blood drawn (about 1 tablespoon) for routine tests at least 3 times a week. If your doctor thinks it is needed, you may have blood drawn more often.

Stem Cell Collection:

Blood stem cells will be collected when your blood counts have returned to normal (about 10-16 days after chemotherapy). The process of stem cell collection takes about 4 hours each time. You will have stem cells collected each day until enough are collected (between 1-6 sessions). A machine is attached to the CVL and blood is withdrawn. The blood then flows through the machine, which removes stem cells from the blood. The blood is then returned back to you through the CVL. The stem cells are then frozen and stored. These stem cells will be given back to you after the next phase of treatment to help your blood counts recover after high dose chemotherapy. After enough stem cells have been collected, you will be admitted to the hospital for high dose chemotherapy. You will sign a separate consent before you receive high dose chemotherapy.

During the stem cell collection, blood (about 2 teaspoons) will be drawn through the CVL to check for cell markers that can affect the response of the cell counts and to check the status of the disease.

Length of Study:

Patients will be followed for up to 12 months after the transplant. You will be taken off study early if the stem cell collection does not work.

This is an investigational study. Etoposide and ifosfamide are FDA approved and are commercially available for lymphomas. Ofatumumab has been approved by the FDA for treatment of recurrent refractory chronic lymphocytic leukemias. G-CSF and Mesna are FDA approved and commercially available. The use of Ofatumumab for the collection of stem cells is investigational.

Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Chemotherapy Plus Ofatumumab Followed by G-CSF for Mobilization of Peripheral Blood Stem Cells in Patients With Non-Hodgkin's Lymphomas
• Actual Study Start Date: Aug 22, 2011
• Actual Primary Completion Date: Jul 21, 2019
• Actual Study Completion Date: Jul 21, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ofatumumab + Stem Cell Collection Ofatumumab 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8. Ifosfamide 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously. Etoposide 150 mg/m2 by vein over 2 hours every 12 hours for 6 doses. Mesna 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts). Mesna 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide). After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose. G-CSF 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis. Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.

Drug: Ofatumumab; 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8; Other Names: Arzera ; Drug: Ifosfamide; 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously.; Other Names: Ifex ; Drug: Etoposide; 150 mg/m2 by vein over 2 hours every 12 hours Days 2, 3, and 4 for 6 doses.; Other Names: VePesid ; Drug: Mesna; 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts) 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide) After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose.; Other Names: Mesnex ; Drug: G-CSF; 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis.; Other Names: Filgrastim Neupogen Granulocyte colony-stimulating factor GCSF ; Procedure: Stem Cell Collection; Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.; Other Names: Apheresis

Outcome Measures

Primary Outcome Measures

1. Mobilization Rate [Mobilization rate measured on Day 21]

   Feasibility of mobilization with ofatumumab + chemotherapy is defined as successful collection of 2 x 10^6CD34+ stem cell/kg and successful purging of the apheresis product of all the markers (i.e., monoclonal B-cells, bcl-2, bcl-1 and/or JH) that were found to be positive on pretreatment evaluation. Mobilization rate is number of participants with successful collection out of total study participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with histologically confirmed CD20 positive B-cell NHL who are candidates for autologous SCT.

2. Patients must have PR to salvage chemotherapy.

3. Age 18-70 years.

4. Platelet count >/= 100,00 mm³ independent of transfusion support.

5. Absolute neutrophil count >/= 1500/mm³.

6. Zubrod performance status (PS) 2 or less.

7. Negative serum pregnancy test in women of childbearing potential. This is a female who has not been postmenopausal for at least 12 consecutive months or who has not undergone previous surgical sterilization.

8. Less than 5% marrow involvement with NHL within 4 weeks of study as defined by unilateral bone marrow aspiration and biopsy.

9. Seronegativity for HIV, HTLV1, Hepatitis .

Exclusion Criteria:

1. Subjects who have current active hepatic ( (HbsAg, HbcAb, and positive viral load by PCR) or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) with ALT > 2x upper limit of normal or bilirubin > 1.5. (Consult with a physician experienced in care and management of subjects with hepatitis B to manage/treat subjects who are anti-HBc positive.)

2. Active CNS disease.

3. Severe concomitant medical or psychiatric illness.

4. Lactating or breast feeding females.

5. Serum creatinine >1.6 mg/dl.

6. History of pelvic radiation.

7. Fludarabine-based chemotherapy within 6 months.

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
• Novartis

Investigators

• Principal Investigator: Issa F. Khouri, MD,BS, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 22, 2019

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Official Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01329900
• Other Study ID Numbers: 2009-0796; NCI-2011-01068
• First Posted: Apr 6, 2011
• Last Update Posted: Jul 8, 2020
• Last Verified: Jun 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: Chemotherapy; Stem Cell Collection; Ofatumumab; Arzerra; Ifosfamide; Ifex; Etoposide; VePesid; Mesna; Mesnex; G-CSF; Filgrastim; Neupogen; Apheresis
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Etoposide; Ifosfamide; Ofatumumab; Lenograstim

Study Results

Participant Flow

Arm/Group Title	Ofatumumab + Stem Cell Collection
Arm/Group Description	Ofatumumab 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8. Ifosfamide 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously. Etoposide 150 mg/m2 by vein over 2 hours every 12 hours for 6 doses. Mesna 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts). Mesna 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide). After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose. G-CSF 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis. Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.
Period Title: Overall Study
STARTED	50
COMPLETED	49
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ofatumumab + Stem Cell Collection
Arm/Group Description	Ofatumumab 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8. Ifosfamide 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously. Etoposide 150 mg/m2 by vein over 2 hours every 12 hours for 6 doses. Mesna 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts). Mesna 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide). After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose. G-CSF 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis. Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.
Overall Participants	50
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	41 82%
>=65 years	9 18%
Sex: Female, Male (Count of Participants)
Female	18 36%
Male	32 64%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 4%
White	46 92%
More than one race	0 0%
Unknown or Not Reported	1 2%
Region of Enrollment (participants) [Number]
United States	50 100%

Outcome Measures

1. Primary Outcome

Title	Mobilization Rate
Description	Feasibility of mobilization with ofatumumab + chemotherapy is defined as successful collection of 2 x 10^6CD34+ stem cell/kg and successful purging of the apheresis product of all the markers (i.e., monoclonal B-cells, bcl-2, bcl-1 and/or JH) that were found to be positive on pretreatment evaluation. Mobilization rate is number of participants with successful collection out of total study participants.
Time Frame	Mobilization rate measured on Day 21

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ofatumumab + Stem Cell Collection
Arm/Group Description	Ofatumumab 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8. Ifosfamide 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously. Etoposide 150 mg/m2 by vein over 2 hours every 12 hours for 6 doses. Mesna 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts). Mesna 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide). After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose. G-CSF 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis. Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.
Measure Participants	50
Count of Participants [Participants]	50 100%

Adverse Events

Time Frame	5 years
Arm/Group Title	Ofatumumab + Stem Cell Collection
Arm/Group Description	Ofatumumab 1000 mg by vein on Day 1 and 2000 mg by vein on Day 8. Ifosfamide 3.33 gm/m2 by vein on Days 2, 3, and 4 continuously. Etoposide 150 mg/m2 by vein over 2 hours every 12 hours for 6 doses. Mesna 2 gm/m2 by vein over 1 hour on Day 2 (given before Ifosfamide starts). Mesna 2.66 gm/m2/day by vein continuous infusion given over 24 hours daily for 3 days starting on Day 2 (together with Ifosfamide). After Ifosfamide/Mesna, 2 gm/m2 by vein given over 12 hours for one dose. G-CSF 6 mcg/kg subcutaneously twice a day on day 6 (rounded off to the nearest vial) until completion of apheresis. Blood stem cells will be collected when blood counts have returned to normal (about 10-16 days after chemotherapy). Stem cell collection takes about 4 hours each time.
All Cause Mortality
	Ofatumumab + Stem Cell Collection
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Serious Adverse Events
	Ofatumumab + Stem Cell Collection
	Affected / at Risk (%)	# Events
Total	1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	1/50 (2%)
Other (Not Including Serious) Adverse Events
	Ofatumumab + Stem Cell Collection
	Affected / at Risk (%)	# Events
Total	48/50 (96%)
Blood and lymphatic system disorders
Febrile neutropenia	6/50 (12%)
Cardiac disorders
Chest pain	1/50 (2%)
Eye disorders
Eye disorders	1/50 (2%)
Gastrointestinal disorders
Abdominal pain	1/50 (2%)
Constipation	6/50 (12%)
Diarrhea	8/50 (16%)
Gastroesophageal reflux disease	2/50 (4%)
Gastrointestinal disorder	3/50 (6%)
Mucositis oral	8/50 (16%)
Nausea	33/50 (66%)
General disorders
Chills	3/50 (6%)
Edema limbs	6/50 (12%)
Fatigue	26/50 (52%)
Fever	1/50 (2%)
Pain	24/50 (48%)
Infections and infestations
Infections and infestations	6/50 (12%)
Injury, poisoning and procedural complications
Bruising	1/50 (2%)
Investigations
Alanine aminotransferase increased	10/50 (20%)
Blood bilirubin increased	2/50 (4%)
Creatinine increased	1/50 (2%)
Metabolism and nutrition disorders
Anorexia	1/50 (2%)
Dehydration	1/50 (2%)
Hypoglycemia	1/50 (2%)
Hypokalemia	1/50 (2%)
Musculoskeletal and connective tissue disorders
Back Pain	1/50 (2%)
Bone pain	9/50 (18%)
Myalgia	2/50 (4%)
Pain in extremity	3/50 (6%)
Nervous system disorders
Dizziness	2/50 (4%)
Facial muscle weakness	1/50 (2%)
Headache	6/50 (12%)
Peripheral sensory neuropathy	2/50 (4%)
Renal and urinary disorders
Acute kidney injury	2/50 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	2/50 (4%)
Dyspnea	7/50 (14%)
Epistaxis	1/50 (2%)
Skin and subcutaneous tissue disorders
Pain of skin	1/50 (2%)
Pruritus	1/50 (2%)
Rash maculo-papular	3/50 (6%)
Vascular disorders
Hypertension	5/50 (10%)
Hypotension	7/50 (14%)

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.