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

Registration Number
NCT03570983
Lead Sponsor
Swedish Medical Center
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...

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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

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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BEAM Regimen- Experimental ArmAllopurinolAllopurinol 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.
BEAM Regimen- Experimental ArmEtoposideAllopurinol 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.
BEAM Regimen- Experimental ArmCarmustineAllopurinol 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.
BEAM Regimen- Experimental ArmCytarabineAllopurinol 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.
Melphalan Regimen- Control ArmAllopurinolMelphalan 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.
Melphalan Regimen- Control ArmMelphalanMelphalan 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.
Primary Outcome Measures
NameTimeMethod
Complete Response Rate12 months

Compare the complete response rates at the time of ASCT following either a high dose BEAM conditioning regimen or a monotherapy Melphalan conditioning regimen

Secondary Outcome Measures
NameTimeMethod
Overall Survival12 months

Measure and compare the Overall Survival between study regimens

Hospitalization Duration12 months

Measure and compare the duration of hospitalization exclusive of high dose regimen between arms

Progression Free Survival12 months

Measure and compare the Progression Free Survival between study regimens

Trial Locations

Locations (1)

Swedish Cancer Institute

🇺🇸

Seattle, Washington, United States

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