Pomalidomide, Dexamethasone and Rituximab in Waldenstrom's Macroglobulinemia

• Sponsor: Steven P. Treon, MD, PhD (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01078974
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 70
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Pomalidomide is a newly discovered drug that may stop cancer cells from growing abnormally. Pomalidomide may also stimulate the immune system to fight the cancer cells and possibly improve the effectiveness of dexamethasone and rituximab to fight the Waldenstrom's Macroglobulinemia (WM) cancer cells. This drug have been used in multiple myeloma and information from these other research studies suggests that Pomalidomide may help to reduce or prevent the growth of cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Waldenstrom's Macroglobulinemia	Drug: pomalidomide; Drug: dexamethasone; Drug: rituximab	Phase 1

Detailed Description

• Participants will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days during which time participants will take Pomalidomide orally once a day. Dexamethasone and rituximab will be administered intravenously on weeks 1, 2, 3, 4 and on weeks 12, 13, 14, 15.

• Since we are looking for the highest dose of Pomalidomide in combination with dexamethasone and rituximab which can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose of the study drug. The dose participants will get will depend on the number of participants who have been enrolled in the study and how well they have tolerated their doses.

• As long as there is no evidence that the participant's Waldenstrom's Macroglobulinemia has progressed, they can continue to receive Pomalidomide for up to 52 weeks. Participants will be asked to return to the clinic for follow-up tests at least every three months for four years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Study of Pomalidomide, Dexamethasone and Rituximab (PDR) in Relapsed or Refractory Waldenstrom's Macroglobulinemia
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pomalidomide, dexamethasone, rituximab Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15	Drug: pomalidomide; Taken orally once a day; Other Names: CC-4047 Pomalyst ; Drug: dexamethasone; Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15; Other Names: Decadron ; Drug: rituximab; Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose of Pomalidomide [2 years]

   To determine the MTD of pomalidomide administered orally in patients with Waldenstrom's Macroglobulinemia in combination with dexamethasone and rituximab. Because maximum tolerated dose was not determined due to study termination, the highest dose of pomalidomide administered is presented below.

2. Tolerability of Pomalidomide [2 years]

   Number of participants with dose limiting toxicities which resulted in being removed from pomalidomide therapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• Able to adhere to the study visit schedule and other protocol requirements

• Clinicopathological diagnosis of Waldenstrom's macroglobulinemia using consensus panel criteria

• CD20 positive based on any previous performed bone marrow immunohistochemistry or flow cytometric analysis

• Meet criteria to treat based on consensus panel criteria

• Patient must have received at least one previous therapy for WM

• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study

• Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of 2 times (or greater) the upper limit of each institution's normal value is required

• ECOG Performance status of 0, 1 or 2

• Laboratory tests within ranges outlined in the protocol

• Disease free of prior malignancies for 5 years or more with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast

• Screening of patients at high risk of HBV or HCV infection

• Willing and able to take aspirin or alternate prophylactic anticoagulants

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness

• Pregnant or lactating females

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Resistance or intolerance to prior rituximab therapy

• Previous therapy with thalidomide or lenalidomide

• Known hypersensitivity to thalidomide, lenalidomide or pomalidomide

• The development of erythema nodosum if characterized by a desquamating rash while taking similar drugs

• Concurrent use of other anti-cancer agents or treatments

• History of non-compliance to medical regimens

• Patients unwilling to or unable to comply with the protocol

• Known positive for HIV or hepatitis infection

• Any history of CVA (Cerebral Vascular Accident/stroke) or clots

• Active DVT or PE that has not been therapeutically anticoagulated

• NYHA classification III and greater heart failure

• Any patient that is unable to ingest or process pomalidomide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Steven P. Treon, MD, PhD
• Celgene Corporation

Investigators

• Principal Investigator: Steven P. Treon, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Steven P. Treon, MD, PhD, Principal Investigator, Dana-Farber/Brigham and Women's Cancer Center
• ClinicalTrials.gov Identifier: NCT01078974
• Other Study ID Numbers: 10-007; PO-WM-PI-0005
• First Posted: Mar 2, 2010
• Last Update Posted: Jul 25, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Steven P. Treon, MD, PhD, Principal Investigator, Dana-Farber/Brigham and Women's Cancer Center: WM; pomalidomide; dexamethasone; rituximab
• Additional relevant MeSH terms: Waldenstrom Macroglobulinemia; Dexamethasone; Rituximab; Pomalidomide

Study Results

Participant Flow

Recruitment Details	A total of 7 participants were recruited at the DFCI medical clinic between 9/22/2010 and 4/3/2012.

Arm/Group Title	Pomalidomide, Dexamethasone, Rituximab
Arm/Group Description	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 pomalidomide: Taken orally once a day dexamethasone: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 rituximab: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
Period Title: Overall Study
STARTED	7
COMPLETED	4
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Pomalidomide, Dexamethasone, Rituximab
Arm/Group Description	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 pomalidomide: Taken orally once a day dexamethasone: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 rituximab: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 57.1%
>=65 years	3 42.9%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	64 (7.27)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	7 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	7 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose of Pomalidomide
Description	To determine the MTD of pomalidomide administered orally in patients with Waldenstrom's Macroglobulinemia in combination with dexamethasone and rituximab. Because maximum tolerated dose was not determined due to study termination, the highest dose of pomalidomide administered is presented below.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The maximum tolerated dose was not determined due to study termination. Three participants experienced IgM flare causing them to be removed from the study early.

Arm/Group Title	Pomalidomide, Dexamethasone, Rituximab
Arm/Group Description	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 pomalidomide: Taken orally once a day dexamethasone: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 rituximab: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
Measure Participants	7
Number [mg]	1

2. Primary Outcome

Title	Tolerability of Pomalidomide
Description	Number of participants with dose limiting toxicities which resulted in being removed from pomalidomide therapy
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pomalidomide, Dexamethasone, Rituximab
Arm/Group Description	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 pomalidomide: Taken orally once a day dexamethasone: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 rituximab: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
Measure Participants	7
Number [participants]	3 42.9%

Adverse Events

Time Frame	Adverse events were collected over a 3 year period.
Arm/Group Title	Pomalidomide, Dexamethasone, Rituximab
Arm/Group Description	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 pomalidomide: Taken orally once a day dexamethasone: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 rituximab: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
All Cause Mortality
	Pomalidomide, Dexamethasone, Rituximab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pomalidomide, Dexamethasone, Rituximab
	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)
Blood and lymphatic system disorders
IgM flare	3/7 (42.9%)	3
Other (Not Including Serious) Adverse Events
	Pomalidomide, Dexamethasone, Rituximab
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Blood and lymphatic system disorders
Anemia	2/7 (28.6%)	2
Neutrophil count decreased	2/7 (28.6%)	3
Platelet count decreased	2/7 (28.6%)	3
Eye disorders
Conjunctivitis	1/7 (14.3%)	1
Gastrointestinal disorders
Diarrhea	2/7 (28.6%)	2
Dyspepsia	1/7 (14.3%)	1
Nausea	2/7 (28.6%)	2
General disorders
Chills	1/7 (14.3%)	1
Cough	1/7 (14.3%)	1
Dyspnea	1/7 (14.3%)	1
Fatigue	1/7 (14.3%)	1
Urinary frequency	1/7 (14.3%)	1
Vomiting	1/7 (14.3%)	1
Infections and infestations
Lung infection	1/7 (14.3%)	1
Tooth Infection	1/7 (14.3%)	1
Injury, poisoning and procedural complications
Infusion related reaction	1/7 (14.3%)	1
Metabolism and nutrition disorders
Alanine aminotransferase increased	1/7 (14.3%)	1
Anorexia	1/7 (14.3%)	1
Aspartate aminotransferase increased	1/7 (14.3%)	1
Creatinine increased	1/7 (14.3%)	1
Hyperglycemia	4/7 (57.1%)	5
Hypocalcemia	1/7 (14.3%)	2
INR increased	1/7 (14.3%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/7 (14.3%)	1
Myalgia	1/7 (14.3%)	1
Neck pain	1/7 (14.3%)	1
Nervous system disorders
Dizziness	1/7 (14.3%)	1
Headache	1/7 (14.3%)	1
Seizure	1/7 (14.3%)	2
Tremor	2/7 (28.6%)	2

Limitations/Caveats

Pomalidomide and rituximab could have a synergistic effect on serum IgM levels and produce an IgM flare. The highest dose of pomalidomide in this trial was 1mg. The study was permanently closed to accrual given the safety concerns with the IgM flare.

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.