Combination Bisphosphonate and Anti-Angiogenesis Therapy With Pamidronate and Thalidomide

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT00083382
• Collaborator: (none)
• Enrollment: 83
• Location: 1
• Arm: 1
• Duration (Months): 185
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this research is to study how helpful the combination of thalidomide and Pamidronate or thalidomide and Zometa is in controlling the myeloma disease and to study any side effects.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Pamidronate; Drug: Thalidomide; Drug: Zometa	Phase 2

Detailed Description

Recently laboratory research found that thalidomide can inhibit the formation of new blood vessels that are necessary for the growth and spread of cancer. In order to grow and increase in size tumors require new blood vessels to supply them with the necessary blood to grow. If we can prevent these new blood vessels feeding the tumor from being formed by using thalidomide we might slow or stop the growth of the tumor. This concept is called "anti-angiogenesis" It is hoped that thalidomide will slow or stop the growth myeloma. However, it cannot be guaranteed that you will benefit if you take part in this study. The treatment you receive may even be harmful.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: UARK 98-036, A Phase II Trial of Combination Bisphosphonate and Anti-Angiogenesis Therapy With Pamidronate and Thalidomide in Patients With Smoldering/Indolent Myeloma
• Study Start Date: Dec 1, 1998
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Thalidomide + Bisphosphonate 200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy

Drug: Pamidronate; Patients will receive either pamidronate or zometa. Pamidronate is administered at a dose of 90 mg by continuous infusion over 90 minutes, every two weeks for 2 months. Disease will be reassessed after two cycles. Those with stable disease or better will receive 90 mg every 4 weeks as maintenance therapy.; Drug: Thalidomide; All Patients will receive thalidomide 200 mg as an oral, once daily dose. Dose may be reduced to as low as 50 mg qod in the event of severe toxicity. Thalidomide will continue daily as tolerated until criteria to remove from study are met. Patients will receive appropriate regimen to prevent constipation (i.e., colace, dulcolax, milk of magnesia, or lactulose); Drug: Zometa; Patients will receive either pamidronate or zometa. Zometa is administered at a dose of 4 mg by continuous infusion every two weeks for 2 months. Disease will be reassessed after two cycles. Those with stable disease or better will receive 4 mg every 4 weeks as maintenance therapy.

Outcome Measures

Primary Outcome Measures

1. Best Response [2 years]

   Best response to study treatment as defined by protocol-specific response criteria: Complete Response (CR) = absence of urine and serum M-components by immunofixation; bone marrow should be adequately cellular (>20%) with <1% monoclonal plasma cells by DNA-clg flow cytometry; serum calcium level must be normal; no new bone lesions nor enlargement of existing lesions; Normalization of serum concentrations of normal immunoglobulins is not required for CR. Partial Response (PR) = Reduction by > 75% in serum myeloma protein production; Decrease in monoclonal marrow plasmacytosis to <5%; Decrease in Bence-Jones proteinuria by >90%; No new lytic bone lesions or soft tissue plasmacytoma. Treatment Failures/Progressive Disease (PD) = Such patients do not fulfill the above criteria and/or have new lytic lesions (but not compression fractures), hypercalcemia, or other new manifestations of disease.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have a diagnosis of Smoldering or Indolent myeloma

• All patients must be informed of the investigational nature of this study and must sign a written informed consent in accordance with UAMS Human Research Advisory Committee and federal guidelines.

Exclusion Criteria:

• Prior bisphosphonate therapy within 30 days prior to study entry.

• Serum creatinine > 5 mg/dl, ascites, or serum direct bilirubin > 2.5 mg/dl.

• Prior plicamycin or calcitonin within 2 weeks of study entry.

• Severe cardiac disease, unstable thyroid disease, or epilepsy.

• Prior radiation therapy to > 20% of the skeleton.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences/MIRT	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas

Investigators

• Principal Investigator: Bart Barlogie, MD, PhD, University of Arkansas

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Myeloma Institute for Research & Therapy

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT00083382
• Other Study ID Numbers: UARK 98-036
• First Posted: May 24, 2004
• Last Update Posted: Jun 24, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by University of Arkansas: Myeloma; Thalidomide; Pamidronate; Aredia; Bisphosphonate; Anti-Angiogenesis; Smoldering/Indolent Myeloma; Zometa
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Pamidronate; Thalidomide

Study Results

Participant Flow

Arm/Group Title	Thalidomide + Bisphosphonate
Arm/Group Description	200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy Thalidomide: All Patients will receive thalidomide 200 mg as an oral once daily dose. Dose may be reduced to as low as 50 mg qod in the event of severe toxicity. Thalidomide will continue daily as tolerated until criteria to remove from study are met. Patients will receive appropriate regimen to prevent constipation (i.e., colace, dulcolax, milk of magnesia, or lactulose) Pamidronate: Patients will receive either pamidronate or zometa. Pamidronate is administered at a dose of 90 mg by continuous infusion over 90 minutes, every two weeks for 2 months. Disease will be reassessed after two cycles. Those with stable disease or better will receive 90 mg every 4 weeks as maintenance therapy. Zometa: Patients will receive either pamidronate or zometa. Zometa is administered at a dose of 4 mg by continuous infusion every two weeks for 2 months. Dise
Period Title: Overall Study
STARTED	83
COMPLETED	83
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Thalidomide + Bisphosphonate
Arm/Group Description	200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
Overall Participants	83
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (9.2)
Sex: Female, Male (Count of Participants)
Female	40 48.2%
Male	43 51.8%

Outcome Measures

1. Primary Outcome

Title	Best Response
Description	Best response to study treatment as defined by protocol-specific response criteria: Complete Response (CR) = absence of urine and serum M-components by immunofixation; bone marrow should be adequately cellular (>20%) with <1% monoclonal plasma cells by DNA-clg flow cytometry; serum calcium level must be normal; no new bone lesions nor enlargement of existing lesions; Normalization of serum concentrations of normal immunoglobulins is not required for CR. Partial Response (PR) = Reduction by > 75% in serum myeloma protein production; Decrease in monoclonal marrow plasmacytosis to <5%; Decrease in Bence-Jones proteinuria by >90%; No new lytic bone lesions or soft tissue plasmacytoma. Treatment Failures/Progressive Disease (PD) = Such patients do not fulfill the above criteria and/or have new lytic lesions (but not compression fractures), hypercalcemia, or other new manifestations of disease.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Thalidomide + Bisphosphonate
Arm/Group Description	200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
Measure Participants	83
Treatment Failure/Progressive Disease	56 67.5%
Partial Response	17 20.5%
Complete Response	10 12%

Adverse Events

Arm/Group Title	Thalidomide + Bisphosphonate
Arm/Group Description	200 mg/day Thalidomide + 90 mg Pamidronate OR 4 mg Zometa every 2 weeks for 2 months and then every 4 weeks as maintenance therapy
All Cause Mortality
	Thalidomide + Bisphosphonate
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Thalidomide + Bisphosphonate
	Affected / at Risk (%)	# Events
Total	16/83 (19.3%)
Cardiac disorders
Cardiovascular-other	3/83 (3.6%)
Syncope	1/83 (1.2%)
Gastrointestinal disorders
Diarrhea without colostomy	1/83 (1.2%)
GI-other	1/83 (1.2%)
General disorders
Fatigue/malaise/lethargy	1/83 (1.2%)
Speech impairment	1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Joint, muscle, bone-other	1/83 (1.2%)
Psychiatric disorders
Confusion	1/83 (1.2%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis/infiltrates	2/83 (2.4%)
Lung-other	1/83 (1.2%)
Respiratory infect w/o neutrop	2/83 (2.4%)
dyspnea	1/83 (1.2%)
Other (Not Including Serious) Adverse Events
	Thalidomide + Bisphosphonate
	Affected / at Risk (%)	# Events
Total	83/83 (100%)
Blood and lymphatic system disorders
Grade 1 Anemia	25/83 (30.1%)
Grade 2 Anemia	8/83 (9.6%)
Grade 1 Neutropenia/granulocytopenia	10/83 (12%)
Grade 2 Neutropenia/granulocytopenia	17/83 (20.5%)
Grade 1 Thrombocytopenia	17/83 (20.5%)
Grade 2 Thrombocytopenia	5/83 (6%)
Grade 3 Thrombocytopenia	5/83 (6%)
Grade 2 Leukopenia	20/83 (24.1%)
Cardiac disorders
Grade 1 Arrhythmia, NOS	9/83 (10.8%)
Grade 4 Cardiovascular - other	4/83 (4.8%)
Grade 1 Edema	27/83 (32.5%)
Grade 2 Edema	8/83 (9.6%)
Grade 1 Hypertension	4/83 (4.8%)
Grade 2 Hypertension	4/83 (4.8%)
Grade 1 Sinus bradycardia	7/83 (8.4%)
Grade 2 Sinus bradycardia	5/83 (6%)
Eye disorders
Grade 2 Blurred vision	12/83 (14.5%)
Grade 1 Eye - other	8/83 (9.6%)
Gastrointestinal disorders
Grade 1 Anorexia	9/83 (10.8%)
Grade 2 Anorexia	5/83 (6%)
Grade 2 Constipation	5/83 (6%)
Grade 1 Constipation/bowel obstruction	24/83 (28.9%)
Grade 2 Constipation/bowel obstruction	32/83 (38.6%)
Grade 3 Constipation/bowel obstruction	4/83 (4.8%)
Grade 1 Diarrhea without colostomy	7/83 (8.4%)
Grade 2 Diarrhea without colostomy	9/83 (10.8%)
Grade 1 GI - other	7/83 (8.4%)
Grade 1 Mouth dryness	12/83 (14.5%)
Grade 2 Mouth dryness	9/83 (10.8%)
Grade 1 Nausea	11/83 (13.3%)
Grade 2 Nausea	8/83 (9.6%)
Grade 1 Vomiting	9/83 (10.8%)
General disorders
Grade 1 Fatigue	23/83 (27.7%)
Grade 2 Fatigue	42/83 (50.6%)
Grade 3 Fatigue	9/83 (10.8%)
Grade 1 Fever without neutropenia	4/83 (4.8%)
Grade 2 Fever without neutropenia	8/83 (9.6%)
Grade 1 Fever, NOS	21/83 (25.3%)
Grade 2 Fever, NOS	12/83 (14.5%)
Grade 2 Sweating	4/83 (4.8%)
Grade 1 weight gain	6/83 (7.2%)
Grade 2 weight gain	5/83 (6%)
Grade 1 weight loss	7/83 (8.4%)
Grade 1 Headache	10/83 (12%)
Grade 2 Headache	7/83 (8.4%)
Grade 1 Somnolence/consciousness loss	9/83 (10.8%)
Grade 2 Somnolence/consciousness loss	5/83 (6%)
Grade 3 Somnolence/consciousness loss	4/83 (4.8%)
Grade 1 Bone Pain	14/83 (16.9%)
Grade 2 Bone Pain	13/83 (15.7%)
Grade 3 Bone Pain	6/83 (7.2%)
Grade 1 Chest pain, not cardio or pleural	4/83 (4.8%)
Grade 2 Lower Back	4/83 (4.8%)
Grade 1 Pain - other	10/83 (12%)
Grade 2 Pain - other	10/83 (12%)
Grade 3 Pain - other	5/83 (6%)
Grade 1 Upper Back	6/83 (7.2%)
Hepatobiliary disorders
Grade 1 Alkaline phosphatase increase	4/83 (4.8%)
Grade 1 Hypoalbuminemia	36/83 (43.4%)
Grade 2 Hypoalbuminemia	7/83 (8.4%)
Grade 1 SGOT (AST) increase	12/83 (14.5%)
Grade 1 SGPT (ALT) increase	19/83 (22.9%)
Immune system disorders
Grade 1 Allergic rhinitis	7/83 (8.4%)
Infections and infestations
Grade 1 Infection w/o 3-4 neutropenia	6/83 (7.2%)
Grade 2 Infection w/o 3-4 neutropenia	9/83 (10.8%)
Grade 2 Respiratory infect w/o neutrop	5/83 (6%)
Metabolism and nutrition disorders
Grade 1 Bicarbonate decrease	19/83 (22.9%)
Grade 1 Hypercalcemia	4/83 (4.8%)
Grade 1 Hyperglycemia	32/83 (38.6%)
Grade 2 Hyperglycemia	11/83 (13.3%)
Grade 3 Hyperglycemia	6/83 (7.2%)
Grade 1 Hypocalcemia	39/83 (47%)
Grade 2 Hypocalcemia	9/83 (10.8%)
Grade 1 Hypokalemia	15/83 (18.1%)
Grade 1 Hypomagnesemia	47/83 (56.6%)
Grade 1 Hyponatremia	24/83 (28.9%)
Grade 3 Hyponatremia	4/83 (4.8%)
Grade 2 Hypophosphatemia	22/83 (26.5%)
Grade 3 Hypophosphatemia	9/83 (10.8%)
Musculoskeletal and connective tissue disorders
Grade 2 Arthritis	6/83 (7.2%)
Grade 1 Joint, muscle, bone - other	21/83 (25.3%)
Grade 2 Joint, muscle, bone - other	16/83 (19.3%)
Grade 3 Joint, muscle, bone - other	4/83 (4.8%)
Grade 1 Muscle Weakness (not neuro)	11/83 (13.3%)
Grade 2 Muscle Weakness (not neuro)	7/83 (8.4%)
Nervous system disorders
Grade 1 Ataxia	4/83 (4.8%)
Grade 1 Cranial neuropathy	6/83 (7.2%)
Grade 1 Dizziness/light headedness	14/83 (16.9%)
Grade 2 Dizziness/light headedness	5/83 (6%)
Grade 3 Dizziness/light headedness	7/83 (8.4%)
Grade 1 Neuro - other	13/83 (15.7%)
Grade 2 Neuro - other	4/83 (4.8%)
Grade 1 Sensory neuropathy	39/83 (47%)
Grade 2 Sensory neuropathy	32/83 (38.6%)
Grade 3 Sensory neuropathy	9/83 (10.8%)
Grade 1 Tremor	12/83 (14.5%)
Grade 2 Tremor	5/83 (6%)
Grade 1 Weakness (motor neuropathy)	15/83 (18.1%)
Grade 2 Weakness (motor neuropathy)	11/83 (13.3%)
Grade 3 Weakness (motor neuropathy)	6/83 (7.2%)
Psychiatric disorders
Grade 1 Anxiety/agitation	10/83 (12%)
Grade 2 Anxiety/agitation	4/83 (4.8%)
Grade 1 Confusion	13/83 (15.7%)
Grade 2 Confusion	5/83 (6%)
Grade 1 Depression	19/83 (22.9%)
Grade 2 Depression	11/83 (13.3%)
Grade 1 Insomnia	5/83 (6%)
Grade 2 Insomnia	5/83 (6%)
Grade 1 Memory loss	6/83 (7.2%)
Grade 1 Mood/consciousness change, NOS	9/83 (10.8%)
Renal and urinary disorders
Grade 1 Creatinine increase	14/83 (16.9%)
Grade 2 Creatinine increase	5/83 (6%)
Grade 1 GU - other	4/83 (4.8%)
Respiratory, thoracic and mediastinal disorders
Grade 1 Cough	7/83 (8.4%)
Grade 2 Cough	6/83 (7.2%)
Grade 2 Dyspnea	19/83 (22.9%)
Grade 3 Dyspnea	5/83 (6%)
Grade 3 Pneumonitis/infiltrates	4/83 (4.8%)
Skin and subcutaneous tissue disorders
Grade 1 Dry skin	10/83 (12%)
Grade 1 Erythema/rash/eruption/desquamation	5/83 (6%)
Grade 2 Erythema/rash/eruption/desquamation	9/83 (10.8%)
Grade 1 Rash/desquamation	10/83 (12%)
Grade 2 Rash/desquamation	7/83 (8.4%)
Grade 1 Skin - other	6/83 (7.2%)
Grade 2 Skin - other	4/83 (4.8%)

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.