A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion

NCT ID: NCT03570983

Last Updated: 2022-06-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-05
• Study Completion Date: 2024-12-31

Brief Summary

The work proposed herein aims to provide the first prospective, randomized comparative efficacy data between Melphalan and BEAM treatment regimen in the Multiple Myeloma (MM) patient population. The risk of such a study is deemed reasonable and ethical since: a) previous works have closely examined the safety and toxicity of the BEAM regimen and the doses to be delivered in this protocol are well below the toxicity levels; b) phase III trials of BEAM have provided reasonable data regarding the efficacy in lymphomas c) Early, retrospective data suggests that BEAM may be efficacious in MM however due to the lack of prospective controlled randomized clinical trial, there is adequate equipoise regarding its efficacy and moreover its comparative efficacy in relation to Melphalan and; D) there are known limitations in the standard-of-care for MM, Melphalan, namely, relatively low rates of complete response at the time of Autologous stem-cell transplantation (ASCT) and poor progression free survival.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

BEAM Regimen- Experimental Arm

Allopurinol Dosage: Allopurinol 200 mg/m2/day starts on the day prior to BCNU, day -8 and stops on day -1.

BCNU (Carmustine) Dosage: Carmustine 300 mg/m2 IV x 1 will be infused over 3 hours on autografting day -7. Carmustine should not be infused with solutions or tubing containing or previously containing bicarbonate solution.

Etoposide (VP-16, Vepesid) Dosage: Etoposide 100 mg/m2 IV BID will be administered in 500-1000 cc normal saline over 2 hours on autografting days -6, -5, -4, and -3 for a total dose of 800 mg/m2. Etoposide may not be infused with sodium bicarbonate solutions.

Cytarabine (Ara-C) Dosage: Cytarabine 100 mg/m2 IV BID will be infused over 3 hours on autografting days -6, -5, -4 and -3.

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

Dosage: Allopurinol 200 mg/m2/day starts on the day prior to BCNU, day -8 and stops on day -1.

Carmustine

Intervention Type: DRUG

Dosage: Carmustine 300 mg/m2 IV x 1 will be infused over 3 hours on autografting day -7. Carmustine should not be infused with solutions or tubing containing or previously containing bicarbonate solution.

Etoposide

Intervention Type: DRUG

Dosage: Etoposide 100 mg/m2 IV BID will be administered in 500-1000 cc normal saline over 2 hours on autografting days -6, -5, -4, and -3 for a total dose of 800 mg/m2. Etoposide may not be infused with sodium bicarbonate solutions.

Cytarabine

Intervention Type: DRUG

Dosage: Cytarabine 100 mg/m2 IV BID will be infused over 3 hours on autografting days -6, -5, -4 and -3. Availability and administration: Cytarabine is available in a reconstituted form in solutions containing 20, 50 and 100 mg of cytarabine per mL.

Melphalan Regimen- Control Arm

Melphalan Dosage: Melphalan will be administered at a dose of 200 mg/m2 IV x 1 infused over 30 minutes on autografting day -2.

Allopurinol Dosage: Allopurinol 200 mg/m2/day starts on the day prior to melphalan (day -3) and stops on day -1.

Group Type: ACTIVE_COMPARATOR

Allopurinol

Intervention Type: DRUG

Dosage: Allopurinol 200 mg/m2/day starts on the day prior to BCNU, day -8 and stops on day -1.

Melphalan

Intervention Type: DRUG

Melphalan will be administered at a dose of 200 mg/m2 IV x 1 infused over 30 minutes on autografting day -2.

Interventions

Allopurinol

Dosage: Allopurinol 200 mg/m2/day starts on the day prior to BCNU, day -8 and stops on day -1.

Intervention Type: DRUG

Carmustine

Dosage: Carmustine 300 mg/m2 IV x 1 will be infused over 3 hours on autografting day -7. Carmustine should not be infused with solutions or tubing containing or previously containing bicarbonate solution.

Intervention Type: DRUG

Etoposide

Dosage: Etoposide 100 mg/m2 IV BID will be administered in 500-1000 cc normal saline over 2 hours on autografting days -6, -5, -4, and -3 for a total dose of 800 mg/m2. Etoposide may not be infused with sodium bicarbonate solutions.

Intervention Type: DRUG

Cytarabine

Dosage: Cytarabine 100 mg/m2 IV BID will be infused over 3 hours on autografting days -6, -5, -4 and -3. Availability and administration: Cytarabine is available in a reconstituted form in solutions containing 20, 50 and 100 mg of cytarabine per mL.

Intervention Type: DRUG

Melphalan

Melphalan will be administered at a dose of 200 mg/m2 IV x 1 infused over 30 minutes on autografting day -2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients who have a new diagnosis of MM according to the International Myeloma Working Group (IMWG) working criteria undergoing autologous or syngeneic hematopoietic transplantation

According to these criteria, the following must be met:

1. Monoclonal plasma cells in the bone marrow > 10% (or proven plasmacytic infiltration in bone marrow biopsy) and/or presence of a biopsy-proven plasmacytoma.

2. Monoclonal protein (M-protein) present in the serum and/or

3. Myeloma-related organ dysfunction (1 or more) of the following. A variety of other types of end-organ dysfunctions can occasionally occur and lead to a need for therapy: - [C] Calcium elevation in the blood, defined as serum calcium > 10.5 mg/dl or upper limit of normal [R] Renal insufficiency (defined as serum creatinine above normal) [A] Anemia, defined as hemoglobin < normal - [B] Lytic bone lesions or osteoporosis. If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) are the sole defining criteria, then > 30% plasma cells are required in the bone marrow

2. Patients must have received initial therapy for MM; at least 2 cycles with a minimum of partial response as defined by IMWG guidelines.

3. Age >=18, < 70years.

4. Karnofsky >70.

5. Life expectancy is not severely limited by concomitant illness based on the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) [8, 9] including:

1. Left ventricular ejection fraction >50%. No uncontrolled arrhythmias or symptomatic cardiac disease.

2. FEV1, FVC and DLCO >50%. No symptomatic pulmonary disease.

3. HIV-negative.

4. Bilirubin <2 mg/dl, SGPT <2.5 x normal.

5. Creatinine clearance > 50 cc/min, estimated or measured.

6. Proficient in English

7. Signed informed consent

Exclusion Criteria

1. Pregnant or lactating females

2. Limited verbal or reading English proficiency

3. Insufficient cognitive or comprehensive capability to provide informed consent

4. Uncontrolled infection

5. Planned tandem autologous/reduced intensity allograft

6. Insufficient peripheral blood stem cells (PBSC) in storage for an autologous transplant (<4.0 x 106 CD34+ cells/kg total).

7. Prior autologous transplant.

8. Patients unwilling to practice adequate forms of contraception if clinically indicated. Male patients on study need to be consulted to use latex condoms even if they have had a vasectomy every time they have sex with a woman who is able to have children

9. Patients with history of seizures

10. Prior history of another malignancy with a life expectancy of <3 years.

11. Known amyloidosis

12. Uncontrolled CNS myeloma

13. Anesthesia Society of America Physical Status (ASA PS) of 4 or greater

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Swedish Cancer Institute

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Janell Duey, JD

Role: CONTACT

Janell.Duey@swedish.org

206-386-2572

John Kaneko

Role: CONTACT

206-386-2370

Facility Contacts

Neil Bailey

Role: primary

neil.bailey@swedish.org

Other Identifiers

STUDY2017000117

Identifier Type: -

Identifier Source: org_study_id